Journal articles: 'Mouse model and breast cancer'

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Wu, Min, and Murray O. Robinson. "Human-in-Mouse breast cancer model." Cell Cycle 8, no. 15 (August 2009): 2317–18. http://dx.doi.org/10.4161/cc.8.15.9206.

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Dabydeen, Sarah A., and Priscilla A. Furth. "Genetically engineered ERα-positive breast cancer mouse models." Endocrine-Related Cancer 21, no. 3 (January 30, 2014): R195—R208. http://dx.doi.org/10.1530/erc-13-0512.

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The majority of human breast cancers are estrogen receptor-positive (ER+), but this has proven challenging to model in genetically engineered mice. This review summarizes information on 21 mouse models that develop ER+ mammary cancer. Where available, information on cancer pathology and gene expression profiles is referenced to assist in understanding which histological subtype of ER+ human cancer each model might represent.ESR1,CCDN1, prolactin,TGFα,AIB1,ESPL1, andWNT1overexpression,PIK3CAgain of function, as well as loss ofP53(Trp53) orSTAT1are associated with ER+ mammary cancer. Treatment with the PPARγ agonist efatutazone in a mouse withBrca1andp53deficiency and 7,12-dimethylbenz(a)anthracene exposure in combination with an activated myristoylated form of AKT1 also induce ER+ mammary cancer. A spontaneous mutant in nude mice that develops metastatic ER+ mammary cancer is included. Age of cancer development ranges from 3 to 26 months and the percentage of cancers that are ER+ vary from 21 to 100%. Not all models are characterized as to their estrogen dependency and/or response to anti-hormonal therapy. Strain backgrounds include C57Bl/6, FVB, BALB/c, 129S6/SvEv, CB6F1, and NIH nude. Most models have only been studied on one strain background. In summary, while a range of models are available for studies of pathogenesis and therapy of ER+ breast cancers, many could benefit from further characterization, and opportunity for development of new models remains.

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Alfred, Jane. "A new mouse model of BRCA1 breast cancer?" Molecular Medicine Today 5, no. 7 (July 1999): 284. http://dx.doi.org/10.1016/s1357-4310(99)01520-8.

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Hennighausen, Lothar. "Mouse models for breast cancer." Oncogene 19, no. 8 (February 2000): 966–67. http://dx.doi.org/10.1038/sj.onc.1203346.

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Burney, Maryam, Lata Mathew, Anjali Gaikwad, Elizabeth K. Nugent, Anneliese O. Gonzalez, and Judith A. Smith. "Evaluation Fucoidan Extracts From Undaria pinnatifida and Fucus vesiculosus in Combination With Anticancer Drugs in Human Cancer Orthotopic Mouse Models." Integrative Cancer Therapies 17, no. 3 (November 20, 2017): 755–61. http://dx.doi.org/10.1177/1534735417740631.

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Objective: To determine the activity of fucoidan from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) when given in combination of chemotherapy drugs using selected human breast or ovarian cancer orthotopic mouse models. Methods: Mice were inoculated with 1 × 106 cells of TOV-112d, MCF-7, or ZR-75 subcutaneously or SKOV3-GFP-Luc intraperitoneally on day 0. MCF-7 and ZR-75 mice were administered with estradiol valerate 2 mg/kg in 0.2 mL castor oil subcutaneously two days prior to cell inoculation. Mice were randomized to one of six arms (N = 10/arm) paclitaxel, UPF/paclitaxel, FVF/paclitaxel, tamoxifen, UPF/tamoxifen, or FVF/tamoxifen. Tumors were measured three times per week for 28 days. Results: Improved activity was observed with UPF or FVF in combination with tamoxifen in both the MCF-7 and ZR-75D breast cancer mouse models. Decreased activity of paclitaxel was observed when given in combination with UPF or FVF in both breast cancer mouse models. The combination of FVF/tamoxifen in the TOV-112d ovarian cancer mouse model had improved activity but no there was difference observed with the UPF/tamoxifen in either ovarian cancer mouse model. No difference was observed with combination of UPF or FVF with paclitaxel in human ovarian cancer SKOV3 or TOV-112d orthotopic mouse models. Conclusion: This study did confirm that UPF/FVF in combination with tamoxifen did not decrease tamoxifen activity in both breast and ovarian cancer, with some potential to improve activity compared to tamoxifen alone in breast cancers. Previous in vitro studies had suggested UPF and FVF had overall synergistic activity with paclitaxel; however, in the current in vivo human cancer mouse model studies there was no change in paclitaxel activity when given in combination with UPF or FVF in either of the two human ovarian cancer models. Furthermore, this study demonstrated that UPF or FVF given in combination with paclitaxel had a potential antagonistic effect in breast cancer models. Additional studies are warranted to delineate mechanisms contributing to variation in the in vivo activity when given in combination with paclitaxel. As a first step, a clinical pharmacokinetic study evaluating impact of FVF/UPF given in combination with chemotherapy in patients with solid tumors is underway.

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Hámori, Lilla, Gyöngyi Kudlik, Kornélia Szebényi, Nóra Kucsma, Bálint Szeder, Ádám Póti, Ferenc Uher, et al. "Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line." International Journal of Molecular Sciences 21, no. 4 (February 11, 2020): 1185. http://dx.doi.org/10.3390/ijms21041185.

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Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. By the age of 80, the estimated risk for breast cancer for women with germline BRCA1 or BRCA2 mutations is around 80%. Genetically engineered BRCA1-deficient mouse models offer a unique opportunity to study the pathogenesis and therapy of triple negative breast cancer. Here we present a newly established Brca1−/−, p53−/− mouse mammary tumor cell line, designated as CST. CST shows prominent features of BRCA1-mutated triple-negative breast cancers including increased motility, high proliferation rate, genome instability and sensitivity to platinum chemotherapy and PARP inhibitors (olaparib, veliparib, rucaparib and talazoparib). Genomic instability of CST cells was confirmed by whole genome sequencing, which also revealed the presence of COSMIC (Catalogue of Somatic Mutations in Cancer) mutation signatures 3 and 8 associated with homologous recombination (HR) deficiency. In vitro sensitivity of CST cells was tested against 11 chemotherapy agents. Tumors derived from orthotopically injected CST-mCherry cells in FVB-GFP mice showed sensitivity to cisplatin, providing a new model to study the cooperation of BRCA1-KO, mCherry-positive tumor cells and the GFP-expressing stromal compartment in therapy resistance and metastasis formation. In summary, we have established CST cells as a new model recapitulating major characteristics of BRCA1-negative breast cancers.

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Son, Yeseon, Changwook Lee, In Tag Yu, Mijin Lee, and Hangun Kim. "Evaluation of Anti-cancer Efficacy of Potassium Usnate using NIR Imaging of Orthotopic Breast Cancer Mouse Model." Yakhak Hoeji 66, no. 5 (October 31, 2022): 278–82. http://dx.doi.org/10.17480/psk.2022.66.5.278.

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Mouse cancer models are useful tools for evaluating in vivo tumor growth and metastasis, providing valuable information for preclinical testing. In this process, optical imaging enables the mouse models to easily identify the progress of disease in a non-invasive way. Here, we established an experimental bioimaging animal model of near-infrared (NIR) fluorescence by using a fluorescence-labeled organism bioimaging instrument (FOBI) and evaluated the anti-cancer effect of potassium usnate (KU) in an orthotopic breast cancer model. The cell viability assay revealed that KU had cytotoxicity with half maximal inhibitory concentration of approximately 138.57, 167.69, and 144.17 μM in 4T1-Fluc-Neo/iRFP-Puro (4T1-iRFP), MDA-MB-231, and MCF-7 cells, respectively. The measurement of NIR fluorescence from the 4T1-iRFP cells in a microtube via FOBI exhibited a strong correlation between cell number and fluorescence intensity, and the minimal detection limit was 10⁵ cells. Accordingly, NIR imaging was performed on the orthotopic breast cancer mouse model by using FOBI, and regression of tumor progression through intraperitoneal KU administration was successfully monitored. Our results demonstrated the establishment of NIR imaging in the orthotopic breast cancer animal model for evaluating the anti-cancer effect of KU.

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Lanari, Claudia, Caroline A. Lamb, Victoria T. Fabris, Luisa A. Helguero, Rocío Soldati, María Cecilia Bottino, Sebastián Giulianelli, Juan Pablo Cerliani, Victoria Wargon, and Alfredo Molinolo. "The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer." Endocrine-Related Cancer 16, no. 2 (June 2009): 333–50. http://dx.doi.org/10.1677/erc-08-0244.

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More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). By contrast, most of the spontaneous, chemically or mouse mammary tumor virus induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which the administration of medroxyprogesterone acetate to BALB/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80%. These tumors are hormone-dependent (HD), metastatic, express both ER and PR, and are maintained by syngeneic transplants. The model has been further refined to include mammary carcinomas that evolve through different stages of hormone dependence, as well as several hormone-responsive cell lines. In this review, we describe the main features of this tumor model, highlighting the role of PR as a trigger of key signaling pathways mediating tumor growth. In addition, we discuss the relevance of this model in comparison with other presently used breast cancer models pointing out its advantages and limitations and how, this model may be suitable to unravel key questions in breast cancer.

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Gkikopoulou, Evi, Anthi Kolokotroni, Vagelis Rinotas, Martina Rauner, and Eleni Douni. "Investigating breast cancer in an osteoporotic TgRANKL mouse model." Bone Reports 16 (May 2022): 101378. http://dx.doi.org/10.1016/j.bonr.2022.101378.

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Cuellar-Vite, Leslie, Kristen L. Weber-Bonk, Fadi W. Abdul-Karim, Christine N. Booth, and Ruth A. Keri. "Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy." Cancers 14, no. 14 (July 11, 2022): 3374. http://dx.doi.org/10.3390/cancers14143374.

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The PI3K/AKT/mTORC1 pathway is a major therapeutic target for many cancers, particularly breast cancer. Everolimus is an mTORC1 inhibitor used in metastatic estrogen receptor-positive (ER+) and epidermal growth factor receptor 2-negative (HER2-) breast cancer. However, mTORC1 inhibitors have limited efficacy in other breast cancer subtypes. We sought to discover collateral sensitivities to mTORC1 inhibition that could be exploited to improve therapeutic response. Using a mouse model of breast cancer that is intrinsically resistant to mTORC1 inhibition, we found that rapamycin alters the expression of numerous extracellular matrix genes, suggesting a potential role for integrins/FAK in controlling mTORC1-inhibitor efficacy. FAK activation was also inversely correlated with rapamycin response in breast cancer cell lines. Supporting its potential utility in patients, FAK activation was observed in >50% of human breast cancers. While blocking FAK in mouse models of breast cancer that are highly responsive to rapamycin had no impact on tumor growth, FAK inhibition sensitized rapamycin-resistant tumors to mTORC1 inhibition. These data reveal an innate dependency on FAK when mTORC1 signaling is lost in tumors that are resistant to mTORC1 inhibitors. They also suggest a precision medicine approach to improving mTORC1 inhibitor efficacy in resistant cancers by suppressing FAK signaling.

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Regua, Angelina T., Austin Arrigo, Daniel Doheny, Grace L. Wong, and Hui-Wen Lo. "Transgenic mouse models of breast cancer." Cancer Letters 516 (September 2021): 73–83. http://dx.doi.org/10.1016/j.canlet.2021.05.027.

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Bennett, L. Michelle, and Roger W. Wiseman. "Mouse models for breast cancer susceptibility." Environmental Toxicology and Pharmacology 4, no. 3-4 (December 1997): 283–88. http://dx.doi.org/10.1016/s1382-6689(97)10024-2.

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Amundadottir, Laufey T., Glenn Merlino, and Robert B. Dickson. "Transgenic mouse models of breast cancer." Breast Cancer Research and Treatment 39, no. 1 (February 1996): 119–35. http://dx.doi.org/10.1007/bf01806083.

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Kim, Ik Soo, and Sung Hee Baek. "Mouse models for breast cancer metastasis." Biochemical and Biophysical Research Communications 394, no. 3 (April 2010): 443–47. http://dx.doi.org/10.1016/j.bbrc.2010.03.070.

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Ye, Genlan, Chuangkun Li, Xiaoliang Zhao, Feng Wen, Leyu Wang, and Xiaozhong Qiu. "A Humanized Cancer-Bone Metastasis Mouse Model Based on Silica Nanoparticles-Incorporated Human Demineralized Bone Matrix." Journal of Biomedical Nanotechnology 15, no. 12 (December 1, 2019): 2363–75. http://dx.doi.org/10.1166/jbn.2019.2860.

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Breast cancer tends to spread to other organs and bone metastasis has the highest frequency in breast cancer metastasis, while its mechanisms are not clear and the current treatments are not very effective. To better study the mechanisms and facilitate drug screening for breast cancer bone metastasis, an in vivo mouse model needs to be constructed. However, the construction of the humanized mouse model for cancer bone metastasis which will mimick real interactions between cancer tissue and bone tissue in the human microenvironment remains a challenge. In this study, we constructed a human engineering bone tissue composed with the human osteoblast-like cells (SaOS-2 cells) and the silica nanoparticlesincorporated human demineralized bone matrix (Si/DBM). The engineered bone was then transplanted into a nude mouse to build a humanized bone microenvironment. The human breast cancer cells were then injected into the fat pads of the nude mouse to form an orthotopic tumor. The results showed that the engineered bone tissue-constructed humanized bone microenvironment had significant advantages when inducing human cancer cells to metastasize into the engineered bone tissue. Further, the SaOS-2/Si/DBM had a stronger ability to entice cancer-bone metastasis through promoting osteogenesis compared to the SaOS-2/DBM. Accordingly, this study highlights a novel, facile and effective mouse model for human cancer-bone metastasis, which will provide a platform to explore the mechanisms and anti-tumor drug screening for cancer-bone metastasis.

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Shrestha, Saroj Kumar, Kyung Hyun Min, Se Woong Kim, Hyoungsu Kim, William H. Gerwick, and Yunjo Soh. "Kalkitoxin: A Potent Suppressor of Distant Breast Cancer Metastasis." International Journal of Molecular Sciences 24, no. 2 (January 7, 2023): 1207. http://dx.doi.org/10.3390/ijms24021207.

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Bone metastasis resulting from advanced breast cancer causes osteolysis and increases mortality in patients. Kalkitoxin (KT), a lipopeptide toxin derived from the marine cyanobacterium Moorena producens (previously Lyngbya majuscula), has an anti-metastatic effect on cancer cells. We verified that KT suppressed cancer cell migration and invasion in vitro and in animal models in the present study. We confirmed that KT suppressed osteoclast-soup-derived MDA-MB-231 cell invasion in vitro and induced osteolysis in a mouse model, possibly enhancing/inhibiting metastasis markers. Furthermore, KT inhibits CXCL5 and CXCR2 expression, suppressing the secondary growth of breast cancer cells on the bone, brain, and lungs. The breast-cancer-induced osteolysis in the mouse model further reveals that KT plays a protective role, judging by micro-computed tomography and immunohistochemistry. We report for the first time the novel suppressive effects of KT on cancer cell migration and invasion in vitro and on MDA-MB-231-induced bone loss in vivo. These results suggest that KT may be a potential therapeutic drug for the treatment of breast cancer metastasis.

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Velazquez, Fabiola N., Leiqing Zhang, Valentina Viscardi, Carolena Trocchia, Yusuf A. Hannun, Lina M. Obeid, and Ashley J. Snider. "Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer." PLOS ONE 16, no. 5 (May 27, 2021): e0252311. http://dx.doi.org/10.1371/journal.pone.0252311.

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Breast cancer is a very heterogeneous disease, and ~30% of breast cancer patients succumb to metastasis, highlighting the need to understand the mechanisms of breast cancer progression in order to identify new molecular targets for treatment. Sphingosine kinase 1 (SK1) has been shown to be upregulated in patients with breast cancer, and several studies have suggested its involvement in breast cancer progression and/or metastasis, mostly based on cell studies. In this work we evaluated the role of SK1 in breast cancer development and metastasis using a transgenic breast cancer model, mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT), that closely resembles the characteristics and evolution of human breast cancer. The results show that SK1 deficiency does not alter tumor latency or growth, but significantly increases the number of metastatic lung nodules and the average metastasis size in the lung of MMTV-PyMT mice. Additionally, analysis of Kaplan-Meier plotter of human disease shows that high SK1 mRNA expression can be associated with a better prognosis for breast cancer patients. These results suggest a metastasis-suppressing function for SK1 in the MMTV-PyMT model of breast cancer, and that its role in regulating human breast cancer progression and metastasis may be dependent on the breast cancer type.

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Kwa, Mei Qi, Rafael Brandao, Trong H. Phung, Jianfeng Ge, Giuseppe Scieri, and Cord Brakebusch. "MRCKα Is Dispensable for Breast Cancer Development in the MMTV-PyMT Model." Cells 10, no. 4 (April 19, 2021): 942. http://dx.doi.org/10.3390/cells10040942.

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MRCKα is a ubiquitously expressed serine/threonine kinase involved in cell contraction and F-actin turnover, which is highly amplified in human breast cancer and part of a gene expression signature for bad prognosis. Nothing is known about the in vivo function of MRCKα. To explore MRCKα function in development and in breast cancer, we generated mice lacking a functional MRCKα gene. Mice were born close to the Mendelian ratio and showed no obvious phenotype including a normal mammary gland formation. Assessing breast cancer development using the transgenic MMTV-PyMT mouse model, loss of MRCKα did not affect tumor onset, tumor growth and metastasis formation. Deleting MRCKα and its related family member MRCKβ in two triple-negative breast cancer cell lines resulted in reduced invasion of MDA-MB-231 cells, but did not affect migration of 4T1 cells. Further genomic analysis of human breast cancers revealed that MRCKα is frequently co-amplified with the oncogenes ARID4B and AKT3 which might contribute to the prognostic value of MRCKα expression. Collectively, these data suggest that MRCKα might be a prognostic marker for breast cancer, but probably of limited functional importance.

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Vila-Leahey, Ava, Sharon Oldford, Paola Marignani, and Jean Marshall. "Histamine receptor 2 blockade reduces breast tumor development and metastasis (TUM9P.1010)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 210.12. http://dx.doi.org/10.4049/jimmunol.194.supp.210.12.

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Abstract Histamine has multiple immunomodulatory roles that impact innate and acquired immunity. Histamine receptor antagonists are widely used clinically to treat allergic disease and gastrointestinal disorders, but their ability to alter effective immune function to breast tumors is unknown. We hypothesized that histamine receptor antagonist treatment could alter immune function in mouse models of breast cancer, therefore altering the growth and spread of breast cancer. Two injectable breast tumor models (the 4T1-BALB/c and E0771-C57BL/6 model) and a spontaneous breast cancer model (STK-/-/NIC model) were utilized. Histamine receptor antagonists were administered in the drinking water prior to tumor cell injection or at time of weaning, respectively. The immune cell populations in the spleen and bone marrow of tumor-bearing mice were analyzed. Ranitidine and famotidine (Hrh2 antagonists) but not selective Hrh1 or Hrh4 antagonists significantly inhibited metastasis in the 4T1 model. Ranitidine treatment also caused significant primary tumor regression in the E0771 breast cancer model. In the STK-/-/NIC model, ranitidine increased latency and decreased the number of tumors per mouse at week 26. Bone marrow and spleen analysis revealed that oral ranitidine treatment significantly and selectively decreased monocyte populations. These studies suggest that HRH2 antagonists may have potential as a beneficial immunomodulatory agent in the prevention or treatment of breast cancer.

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Shigehiro, Tsukasa, Maho Ueno, Mayumi Kijihira, Ryotaro Takahashi, Chiho Umemura, Eman A. Taha, Chisaki Kurosaka, et al. "Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model." International Journal of Molecular Sciences 23, no. 19 (September 20, 2022): 11035. http://dx.doi.org/10.3390/ijms231911035.

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Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-γ production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-γ expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103+CD11b+ dendritic cells (DCs) into the mLN, along with increased (1→3)-β-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103+CD11b+ DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development.

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Doornebal, Chris W., Sjoerd Klarenbeek, Tanya M. Braumuller, Christiaan N. Klijn, Metamia Ciampricotti, Cheei-Sing Hau, Markus W. Hollmann, Jos Jonkers, and Karin E. de Visser. "A Preclinical Mouse Model of Invasive Lobular Breast Cancer Metastasis." Cancer Research 73, no. 1 (November 14, 2012): 353–63. http://dx.doi.org/10.1158/0008-5472.can-11-4208.

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Brown, Powel H., Abhijit Mazumdar, William Tahaney, Jamal Hill, Yun Zhang, Sumankalai Ramachandran, Jitesh Kawedia, et al. "Abstract IA017: Targeting the mTOR pathway for the prevention of triple-negative breast cancer." Cancer Prevention Research 16, no. 1_Supplement (January 1, 2023): IA017. http://dx.doi.org/10.1158/1940-6215.precprev22-ia017.

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Abstract Phase III cancer prevention clinical trials have shown that breast cancer prevention is feasible using anti-estrogen drugs. However, these drugs have not been widely accepted because of concerns about toxicity. In addition, anti-estrogen drugs do not prevent estrogen-negative breast cancers, including the most aggressive form of breast cancer, triple-negative breast cancer (TNBC), that does not express the estrogen receptor (ER), progesterone receptor, or the human epidermal growth factor receptor 2 (HER2). Our laboratory is focused on identifying growth-regulatory molecules that are essential for the growth of TNBCs. For this study, we identified mTOR as an essential growth-regulatory molecule that is highly expressed in TNBCs. We then investigated whether the mTOR inhibitor everolimus can prevent mammary tumors in transgenic mouse models including 4 models of TNBC and one model of ER-negative/HER2-positive breast cancer. Everolimus treatment significantly delayed mammary tumor formation but with a varying degree in all five mouse models. Everolimus treatment for up to 1 year was well tolerated with no observable toxicity. These results suggest that mTOR inhibitors may be promising drugs for the prevention of ER-negative and triple-negative breast cancers in women at risk of these aggressive breast cancers. Grant support: This research was supported by an NCI-PREVENT contract to P. Brown and A. Mazumdar (HHSN261201500018I/HHSN26100006). Citation Format: Powel H. Brown, Abhijit Mazumdar, William Tahaney, Jamal Hill, Yun Zhang, Sumankalai Ramachandran, Jitesh Kawedia, Jing Qian, Alejandra Contreras, Michelle Savage, Lana Vornik. Targeting the mTOR pathway for the prevention of triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA017.

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Yan, Leqin, Sally Gaddis, Luis Della Coletta, John Repass, Katherine Leslie Powell, Melissa S. Simper, Yueping Chen, et al. "ATF3-Induced Mammary Tumors Exhibit Molecular Features of Human Basal-Like Breast Cancer." International Journal of Molecular Sciences 22, no. 5 (February 26, 2021): 2353. http://dx.doi.org/10.3390/ijms22052353.

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Basal-like breast cancer (BLBC) is an aggressive and deadly subtype of human breast cancer that is highly metastatic, displays stem-cell like features, and has limited treatment options. Therefore, developing and characterizing preclinical mouse models with tumors that resemble BLBC is important for human therapeutic development. ATF3 is a potent oncogene that is aberrantly expressed in most human breast cancers. In the BK5.ATF3 mouse model, overexpression of ATF3 in the basal epithelial cells of the mammary gland produces tumors that are characterized by activation of the Wnt/β-catenin signaling pathway. Here, we used RNA-Seq and microRNA (miRNA) microarrays to better define the molecular features of BK5.ATF3-derived mammary tumors. These analyses showed that these tumors share many characteristics of human BLBC including reduced expression of Rb1, Esr1, and Pgr and increased expression of Erbb2, Egfr, and the genes encoding keratins 5, 6, and 17. An analysis of miRNA expression revealed reduced levels of Mir145 and Mir143, leading to the upregulation of their target genes including both the pluripotency factors Klf4 and Sox2 as well as the cancer stem-cell-related gene Kras. Finally, we show through knock-down experiments that ATF3 may directly modulate MIR145/143 expression. Taken together, our results indicate that the ATF3 mouse mammary tumor model could provide a powerful model to define the molecular mechanisms leading to BLBC, identify the factors that contribute to its aggressiveness, and, ultimately, discover specific genes and gene networks for therapeutic targeting.

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Arafat, Kholoud, Elham Al Kubaisy, Shahrazad Sulaiman, Sherif M. Karam, Zeina Al Natour, Ahmed H. Hassan, and Samir Attoub. "SMARCAD1 in Breast Cancer Progression." Cellular Physiology and Biochemistry 50, no. 2 (2018): 489–500. http://dx.doi.org/10.1159/000494163.

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Background/Aims: Breast cancer is the most common cancer in women worldwide, and within this cancer type, triple-negative breast cancers have the worst prognosis. The identification of new genes associated with triple-negative breast cancer progression is crucial for developing more specific anti-cancer targeted therapies, which could lead to a better management of these patients. In this context, we have recently demonstrated that SMARCAD1, a DEAD/H box-containing helicase, is involved in breast cancer cell migration, invasion, and metastasis. The aim of this study was to investigate the impact of the stable knockdown of SMARCAD1 on human breast cancer cell progression. Methods: Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of the stable knockdown of SMARCAD1 on human breast cancer cell proliferation and colony growth in vitro and on tumour growth in chick embryo and nude mouse xenograft models in vivo using MDA-MB-231 (ER-/PR-/ HER2-) and T47D (ER+/PR+/-/HER2-) human breast cancer cell lines. Results: We found that SMARCAD1 knockdown resulted in a significant decrease in breast cancer cell proliferation and colony formation, leading to the significant inhibition of tumour growth in both the chick embryo and nude mouse xenograft models. This inhibition was due, at least in part, to a decrease in IKKβ expression. Conclusion: These results indicate that SMARCAD1 is involved in breast cancer progression and can be a promising target for breast cancer therapy.

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Zou, Yiyu, Susan Fineberg, Alexander Pearlman, Richard D. Feinman, and Eugene J. Fine. "The effect of a ketogenic diet and synergy with rapamycin in a mouse model of breast cancer." PLOS ONE 15, no. 12 (December 3, 2020): e0233662. http://dx.doi.org/10.1371/journal.pone.0233662.

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Background The effects of diet in cancer, in general, and breast cancer in particular, are not well understood. Insulin inhibition in ketogenic, high fat diets, modulate downstream signaling molecules and are postulated to have therapeutic benefits. Obesity and diabetes have been associated with higher incidence of breast cancer. Addition of anti-cancer drugs together with diet is also not well studied. Methods Two diets, one ketogenic, the other standard mouse chow, were tested in a spontaneous breast cancer model in 34 mice. Subgroups of 3–9 mice were assigned, in which the diet were implemented either with or without added rapamycin, an mTOR inhibitor and potential anti-cancer drug. Results Blood glucose and insulin concentrations in mice ingesting the ketogenic diet (KD) were significantly lower, whereas beta hydroxybutyrate (BHB) levels were significantly higher, respectively, than in mice on the standard diet (SD). Growth of primary breast tumors and lung metastases were inhibited, and lifespans were longer in the KD mice compared to mice on the SD (p<0.005). Rapamycin improved survival in both mouse diet groups, but when combined with the KD was more effective than when combined with the SD. Conclusions The study provides proof of principle that a ketogenic diet a) results in serum insulin reduction and ketosis in a spontaneous breast cancer mouse model; b) can serve as a therapeutic anti-cancer agent; and c) can enhance the effects of rapamycin, an anti-cancer drug, permitting dose reduction for comparable effect. Further, the ketogenic diet in this model produces superior cancer control than standard mouse chow whether with or without added rapamycin.

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Chen, Leilei, Xueying Yang, Likun Zhang, Xiaobo Chen, Henry Q. X. Li, and Jingjing Wang. "Abstract 3115: Establishment and characterization of patient-derived breast cancer models for cancer studies." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3115. http://dx.doi.org/10.1158/1538-7445.am2022-3115.

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Abstract BACKGROUND: Despite the progress and development of targeted agents and Immunotherapeutics, breast cancer is still the leading cause of death among women worldwide. At present, targeted therapy for breast cancers include endocrine blockage therapy for estrogen receptor positive (ER+) tumors and trastuzumab or lapatinib for HER2 positive (HER2+) tumors and CDK inhibitors for HER negative (HER-) tumors as well as PARP inhibitors for BRCA1/2 mutations. There is still a high unmet need for triple negative breast cancer (TNBC) and relapsed breast cancers with specific mutations. Breast cancer is a highly heterogeneous disease and reliable breast cancer models are needed to develop new clinical therapies and better reflect tumor biology. Patient-derived xenograft (PDX) models have been widely used for understanding tumor characteristics and represent human heterogeneity more faithfully and thus are suitable for mouse clinical studies for predicting drug efficacy in the clinic. Here we report the establishment and characterization of a panel of breast cancer (BC) PDX for preclinical research. METHODS: Tumor samples from patients’ breast tumor or metastastic lesion obtained via surgery, biopsy, or pleural effusions/ascites were engrafted subcutaneously in immunodeficient mice to establish PDX models. The models were classified and characterized by histopathology, immunohistochemistry (IHC), and breast cancer specific biomarkers such as estrogen receptor (ER), progesterone receptor (PR) and HER2. Genomic analysis of these models was performed by next generation sequencing (NGS). In these breast cancer models, the effects of estrogen on tumor growth and targeted endocrine therapy such as Fulvestrant were evaluated. The change of tumor volume over time was used to determine the growth rate and response to treatment in mice. RESULTS: A series of BC PDX models derived from primary patient breast tumor or metastatic lesions were successfully established and characterized. Key characteristics of parental tumors, such as histopathology, clinical markers, gene expression and copy number, as well as estrogen dependence was retained. The IHC data indicated various expression levels of ER, PR and HER2 across the panel, with TNBC being the dominant subtype. ESR1 mutation, which may play an important role in BC progression and endocrine therapy resistance, was also identified in an estrogen-independent model. In vivo, these models showed distinct tumor growth rates and different pharmacodynamic responses to standard of care agents. For example, ESR1 mutant model was responsive to Fulvestrant. CONCLUSIONS: The established BC PDX panel represent a range or ER/PR/HER2 expression status from primary and advanced cancer providing a series of preclinical models for breast cancer research and potential for mouse clinical trial enrollment. Citation Format: Leilei Chen, Xueying Yang, Likun Zhang, Xiaobo Chen, Henry Q.X. Li, Jingjing Wang. Establishment and characterization of patient-derived breast cancer models for cancer studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3115.

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Potter, David A., Douglas Yee, Zhijun Guo, and Mariangellys Rodriguez. "Should diabetic women with breast cancer have their own intervention studies?" Endocrine-Related Cancer 19, no. 1 (December 16, 2011): C13—C17. http://dx.doi.org/10.1530/erc-11-0309.

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This commentary on ‘Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a mouse model of postmenopausal obesity’ by Nogueiraet al., published in this issue ofEndocrine-Related Cancer, addresses the challenges of translating diet, exercise, and pharmacologic trials in diabetic mouse mammary tumor models to human studies. We propose that trials specifically designed to test such interventions in diabetic women with breast cancer would be valuable and informative.

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Rivina, Leena, Michael Davoren, and Robert H. Schiestl. "Mouse Models for Radiation-Induced Breast Cancer." Cancer and Oncology Research 2, no. 6 (September 2014): 80–86. http://dx.doi.org/10.13189/cor.2014.020602.

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Hutchinson, John N., and William J. Muller. "Transgenic mouse models of human breast cancer." Oncogene 19, no. 53 (December 2000): 6130–37. http://dx.doi.org/10.1038/sj.onc.1203970.

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Jonkers, J. "201 Mouse Models of Metastatic Breast Cancer." European Journal of Cancer 48 (March 2012): S102. http://dx.doi.org/10.1016/s0959-8049(12)70269-1.

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Shi, Guilan, Xiufen Zhuang, Yanhong Wu, and Richard Heller. "IFN-γ inhibit ALDHbr breast cancer cells in murine 4T1 tumor model." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 194.25. http://dx.doi.org/10.4049/jimmunol.202.supp.194.25.

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Abstract Background Due to the heterogeneity of breast cancer cells, cytotoxic treatments targeting proliferative cancer cells could not eradicate all cancer cells. Compelling evidence suggests that breast cancer stem cells (BCSCs) have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation, relapse, metastasis, and chemo-resistance. Cytokines in the tumor microenvironment can regulate the self-renewal and survival of BCSCs in a variety of ways. Methods and Results We have utilized in vitro and mouse xenograft models (immunocompetent Balb/c mice and thymus-deficient nude mice (Balb/c nude)) to examine the interaction between breast cancer stem cells (BCSCs) and T cells or cytokine IFN-γ. In vitro assay, such as migration and invasion and sphere-forming, we demonstrate that CD8+ T lymphocytes regulate aldehyde dehydrogenase (ALDH) expressing in BCSCs (ALDHbr 4T1 cells) may through cytokine IFN-γ. Utilizing immunocytochemistry, western blotting and gene expression microarray of ALDHbr vs ALDHdim 4T1 cells, we identified cytokine IFN-γ decreased ALDH1A protein expression and regulated the cancer stem cell population. In various in vivo-like screening assays, depletion of either CD4+ or CD8+ T cells associated with increased proportions of BCSCs. Conclusion The collective results suggest that IFN-γ as a highly secreted cytokine may affect cancer stem cells in mouse breast cancer model.

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Utama, F. E., M. J. LeBaron, L. M. Neilson, A. S. Sultan, A. F. Parlow, K.-U. Wagner, and H. Rui. "Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice." Journal of Endocrinology 188, no. 3 (March 2006): 589–601. http://dx.doi.org/10.1677/joe.1.06560.

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Experimental testing of growth, metastatic progression and drug responsiveness of human breast cancer in vivo is performed in immunodeficient mice. Drug candidates need to show promise against human breast cancer in mice before being allowed into clinical trials. Breast cancer growth is under endocrine control by ovarian steroids and the pituitary peptide hormone prolactin. While it is recognized that the most relevant biologic effects of prolactin are achieved with prolactin from the matching species, the biologic efficacy of mouse prolactin for human prolactin receptors has not been recorded. Thus, it is unclear whether the mouse endocrine environment adequately reflects the hormonal environment in breast cancer patients with regard to prolactin. We now show both recombinant and natural pituitary-derived mouse prolactin to be a poor agonist for human prolactin receptors. Mouse prolactin failed to induce human prolactin receptor-mediated biologic responses of cell clustering, proliferation, gene induction and signal transduction, including activation of Stat5, Stat3, Erk1/2 and Akt pathways. Consistent data were derived from human breast cancer lines T-47D, MCF-7 and ZR-75.1, as well as human prolactin receptor-transfected COS-7 and 32D cells. Failure of mouse prolactin to activate human prolactin receptors uncovers a key deficiency of the mouse endocrine environment for human xenotransplant studies. Since most human breast cancers express prolactin receptors, human breast cancer transferred into mice is unnaturally selected for growth in the absence of circulating prolactin. The new insight raises concerns about the validity of analyzing biology and drug responsiveness of human breast cancer in existing mouse xenotransplant models.

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Liu, Peng, Hailin Tang, Jiali Wu, Xingsheng Qiu, Yanan Kong, Lijuan Zhang, Xinhua Xie, and Xiangsheng Xiao. "Linc01638 Promotes Tumorigenesis in HER2+ Breast Cancer." Current Cancer Drug Targets 19, no. 1 (December 13, 2018): 74–80. http://dx.doi.org/10.2174/1568009618666180709163718.

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Background: Long non-coding RNAs play crucial roles in various biological activities and diseases. The role of long intergenic non-coding RNA01638 (linc01638) in breast cancer, especially in HER2-positive breast cancer, remains largely unknown. Objective: To investigate the effect of linc01638 on tumorigenesis in HER2-positive breast cancer. </P><P> Methods: We first used qRT-PCR to detect linc01638 expression in HER2-positive breast cancer cells and tissues. Then we analyzed the effects of linc01638 expression in HER2-positive breast cancer cells through cell apoptosis assay, cell proliferation assay, colony formation assay, and cell invasion assay. We conducted mouse xenograft model to further confirm the role of linc01638 in HER2-positive breast cancer. Moreover, we used Western blot and IHC analysis to access the effect of linc01638 on DNMTs, BRCA1 and PTEN expressions in transplanted tumors. Results: Linc01638 was found to be remarkably overexpressed in HER2-positive breast cancer cells and tissues. Suppression of linc01638 enhanced cell apoptosis, as well as inhibited the growth and invasiveness of HER2-positive breast cancer cells in vitro and tumor progression and metastasis in vivo. Furthermore, inhibition of linc01638 by shRNA attenuated expression of DNMT1, DNMT3a, and DNMT3b, and promoted expression of BRCA1 and PTEN in HER2-positive breast cancer cells and mouse xenograft models. Linc01638 might be a promising biomarker and therapeutic target for treatment of HER2-positive breast cancer.

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Li, Juan, Dominique Davidson, Cleiton Martins Souza, Ming-Chao Zhong, Ning Wu, Morag Park, William J. Muller, and André Veillette. "Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition." Molecular and Cellular Biology 35, no. 23 (September 21, 2015): 4069–82. http://dx.doi.org/10.1128/mcb.00741-15.

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PTPN12 is a cytoplasmic protein tyrosine phosphatase (PTP) reported to be a tumor suppressor in breast cancer, through its capacity to dephosphorylate oncogenic receptor protein tyrosine kinases (PTKs), such as ErbB2. However, the precise molecular and cellular impact of PTPN12 deficiency in breast cancer progression remains to be fully clarified. Here, we addressed this issue by examining the effect of PTPN12 deficiency on breast cancer progressionin vivo, in a mouse model of ErbB2-dependent breast cancer using a conditional PTPN12-deficient mouse. Our studies showed that lack of PTPN12 in breast epithelial cells accelerated breast cancer development and lung metastasesin vivo. PTPN12-deficient breast cancer cells displayed enhanced tyrosine phosphorylation of the adaptor Cas, the adaptor paxillin, and the kinase Pyk2. They exhibited no detectable increase in ErbB2 tyrosine phosphorylation. PTPN12-deficient cells were more resistant to anoikis and had augmented migratory and invasive properties. Enhanced migration was corrected by inhibiting Pyk2. PTPN12-deficient breast cancer cells also acquired partial features of epithelial-to-mesenchymal transition (EMT), a feature of more aggressive forms of breast cancer. Hence, loss of PTPN12 promoted tumor progression in a mouse model of breast cancer, supporting the notion that PTPN12 is a tumor suppressor in human breast cancer. This function was related to the ability of PTPN12 to suppress cell survival, migration, invasiveness, and EMT and to inhibit tyrosine phosphorylation of Cas, Pyk2, and paxillin. These findings enhance our understanding of the role and mechanism of action of PTPN12 in the control of breast cancer progression.

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Gwynne, William D., Mirza S. Shakeel, Adele Girgis-Gabardo, and John A. Hassell. "The Role of Serotonin in Breast Cancer Stem Cells." Molecules 26, no. 11 (May 26, 2021): 3171. http://dx.doi.org/10.3390/molecules26113171.

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Breast tumors were the first tumors of epithelial origin shown to follow the cancer stem cell model. The model proposes that cancer stem cells are uniquely endowed with tumorigenic capacity and that their aberrant differentiation yields non-tumorigenic progeny, which constitute the bulk of the tumor cell population. Breast cancer stem cells resist therapies and seed metastases; thus, they account for breast cancer recurrence. Hence, targeting these cells is essential to achieve durable breast cancer remissions. We identified compounds including selective antagonists of multiple serotonergic system pathway components required for serotonin biosynthesis, transport, activity via multiple 5-HT receptors (5-HTRs), and catabolism that reduce the viability of breast cancer stem cells of both mouse and human origin using multiple orthologous assays. The molecular targets of the selective antagonists are expressed in breast tumors and breast cancer cell lines, which also produce serotonin, implying that it plays a required functional role in these cells. The selective antagonists act synergistically with chemotherapy to shrink mouse mammary tumors and human breast tumor xenografts primarily by inducing programmed tumor cell death. We hypothesize those serotonergic proteins of diverse activity function by common signaling pathways to maintain cancer stem cell viability. Here, we summarize our recent findings and the relevant literature regarding the role of serotonin in breast cancer.

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Bimonte, Sabrina, Antonio Barbieri, Domenica Rea, Giuseppe Palma, Antonio Luciano, Arturo Cuomo, Claudio Arra, and Francesco Izzo. "Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression." BioMed Research International 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/161508.

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Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Severalin vitroandin vivostudies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performedin vitrostudies on ER-negative human breast carcinoma cells, MDA.MB231 andin vivostudies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphinein vitroenhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells.In vivostudies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression.

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Olukoya, Ayodeji, Shaymaa Bahnassy, Nicole S. Spoelstra, Lu Jin, Suman Ranjit, Anthony Elias, Jennifer K. Richer, and Rebecca B. Riggins. "Abstract 1639: Human immune system mouse model of ER+ metastatic breast cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 1639. http://dx.doi.org/10.1158/1538-7445.am2022-1639.

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Abstract In a recent clinical trial in heavily pretreated estrogen receptor alpha-positive (ER+) metastatic breast cancer (MBC), ~23% of patients reached the primary endpoint of clinical benefit of >24 weeks on Fulvestrant plus the anti-androgen Enzalutamide. ESR1 mutant biopsies had more T regulatory cells (t test p<0.021) and macrophages (p<0.003) than ESR1 wild type (WT), which had more TP53 mutations and higher levels of cytotoxic T effector cells (p<0.01). In addition, PD-L1 increased in post- vs. pre-treatment biopsies (paired t test p<0.002). This increase in PD-L1 post-treatment warrants testing if the addition of a checkpoint inhibitor to the Fulvestrant-Enzalutamide combination will enhance therapy efficacy in ER+ MBC resistant to standard endocrine therapy. However, the lack of immune competent ER+ breast cancer pre-clinical models is a major barrier to these studies. Human immune system (HIS) mouse models were developed as a platform in which to test immune checkpoint inhibitors in other human cancers, and one HIS model was recently shown to support the growth and immune infiltration of ER+ patient-derived xenograft (PDX) primary tumors. We tested whether HIS mice are a robust model in which to define ER+ tumor-immune microenvironment interactions at metastatic sites. We implanted NCG mice (NOD-Prkdcem26Cd52Il2rgem26Cd22/NjuCrl) humanized by engraftment of human umbilical cord blood-derived CD34+ (huCD34+) stem cells with the estrogen-independent HCI-013EI (013EI) PDX, derived from an ER+, invasive lobular MBC which harbors the Y537S ESR1 mutation. Mice were monitored for tumor latency and growth rate, and primary tumors and organs were collected for immunohistochemistry, single-cell RNA sequencing (scRNAseq), and phasor-fluorescence lifetime imaging microscopy (FLIM). The ER mutated PDX 013EI had a longer tumor latency in HIS (median 77 days) vs. age-matched immune deficient control mice (27.5 days, log-rank p=0.043). Once formed, 013EI tumors in HIS mice grew slower than those in controls (mixed-effects analysis, p=0.035). HIS mice had visible lung, liver, and/or gastrointestinal tract metastases despite small primary tumors. Lung metastases from HIS mice retain ER expression and are infiltrated by human CD4+, CD8+, and CD68+ immune cells. Initial scRNAseq analysis also suggests infiltration by diverse immune cell populations in primary tumors from HIS mice. Initial phasor-FLIM for NADH autofluorescence suggests that 013EI tumors are highly glycolytic in HIS mice. In conclusion, our results show that huCD34+ HIS mice effectively support growth, metastasis, and immune infiltration of an ESR1 mutant MBC PDX. Ongoing studies will further define the tumor-immune microenvironment in this and ESR1 WT MBC PDX, focusing on immune cell infiltration, PD-L1 expression, steroid receptor status, metabolic signaling and changes in these parameters following novel combinations of endocrine, immunotherapy and metabolic agents. Citation Format: Ayodeji Olukoya, Shaymaa Bahnassy, Nicole S. Spoelstra, Lu Jin, Suman Ranjit, Anthony Elias, Jennifer K. Richer, Rebecca B. Riggins. Human immune system mouse model of ER+ metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1639.

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Henneman, Linda, Martine H. van Miltenburg, Ewa M. Michalak, Tanya M. Braumuller, Janneke E. Jaspers, Anne Paulien Drenth, Renske de Korte-Grimmerink, et al. "Selective resistance to the PARP inhibitor olaparib in a mouse model for BRCA1-deficient metaplastic breast cancer." Proceedings of the National Academy of Sciences 112, no. 27 (June 22, 2015): 8409–14. http://dx.doi.org/10.1073/pnas.1500223112.

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Metaplastic breast carcinoma (MBC) is a rare histological breast cancer subtype characterized by mesenchymal elements and poor clinical outcome. A large fraction of MBCs harbor defects in breast cancer 1 (BRCA1). As BRCA1 deficiency sensitizes tumors to DNA cross-linking agents and poly(ADP-ribose) polymerase (PARP) inhibitors, we sought to investigate the response of BRCA1-deficient MBCs to the PARP inhibitor olaparib. To this end, we established a genetically engineered mouse model (GEMM) for BRCA1-deficient MBC by introducing the MET proto-oncogene into a BRCA1-associated breast cancer model, using our novel female GEMM ES cell (ESC) pipeline. In contrast to carcinomas, BRCA1-deficient mouse carcinosarcomas resembling MBC show intrinsic resistance to olaparib caused by increased P-glycoprotein (Pgp) drug efflux transporter expression. Indeed, resistance could be circumvented by using another PARP inhibitor, AZD2461, which is a poor Pgp substrate. These preclinical findings suggest that patients with BRCA1-associated MBC may show poor response to olaparib and illustrate the value of GEMM-ESC models of human cancer for evaluation of novel therapeutics.

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Welm, Alana L., Julie B. Sneddon, Carmen Taylor, Dimitry S. A. Nuyten, Marc J. van de Vijver, Bruce H. Hasegawa, and J. Michael Bishop. "The macrophage-stimulating protein pathway promotes metastasis in a mouse model for breast cancer and predicts poor prognosis in humans." Proceedings of the National Academy of Sciences 104, no. 18 (April 24, 2007): 7570–75. http://dx.doi.org/10.1073/pnas.0702095104.

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A better understanding of tumor metastasis requires development of animal models that authentically reproduce the metastatic process. By modifying an existing mouse model of breast cancer, we discovered that macrophage-stimulating protein promoted breast tumor growth and metastasis to several organs. A special feature of our findings was the occurrence of osteolytic bone metastases, which are prominent in human breast cancer. To explore the clinical relevance of our model, we examined expression levels of three genes involved in activation of the MSP signaling pathway (MSP, MT-SP1, and MST1R) in human breast tumors. We found that overexpression of MSP, MT-SP1, and MST1R was a strong independent indicator of both metastasis and death in human breast cancer patients and significantly increased the accuracy of an existing gene expression signature for poor prognosis. These data suggest that signaling initiated by MSP is an important contributor to metastasis of breast cancer and introduce an independent biomarker for assessing the prognosis of humans with breast cancer.

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Singh, Sharda P., Jihyun Lee, Chhanda Bose, Hongzhi Li, Yate-Ching Yuan, Ashly Hindle, Sharad S. Singhal, et al. "Haploinsufficiency Interactions between RALBP1 and p53 in ERBB2 and PyVT Models of Mouse Mammary Carcinogenesis." Cancers 13, no. 13 (July 2, 2021): 3329. http://dx.doi.org/10.3390/cancers13133329.

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We recently reported that loss of one or both alleles of Ralbp1, which encodes the stress-protective protein RLIP76 (Rlip), exerts a strong dominant negative effect on both the inherent cancer susceptibility and the chemically inducible cancer susceptibility of mice lacking one or both alleles of the tumor suppressor p53. In this paper, we examined whether congenital Rlip deficiency could prevent genetically-driven breast cancer in two transgenic mouse models: the MMTV-PyVT model, which expresses the polyomavirus middle T antigen (PyVT) under control of the mouse mammary tumor virus promoter (MMTV) and the MMTV-Erbb2 model which expresses MMTV-driven erythroblastic leukemia viral oncogene homolog 2 (Erbb2, HER2/Neu) and frequently acquires p53 mutations. We found that loss of either one or two Rlip alleles had a suppressive effect on carcinogenesis in Erbb2 over-expressing mice. Interestingly, Rlip deficiency did not affect tumor growth but significantly reduced the lung metastatic burden of breast cancer in the viral PyVT model, which does not depend on either Ras or loss of p53. Furthermore, spontaneous tumors of MMTV-PyVT/Rlip+/+ mice showed no regression following Rlip knockdown. Finally, mice lacking one or both Rlip alleles differentially expressed markers for apoptotic signaling, proliferation, angiogenesis, and cell cycling in PyVT and Erbb2 breast tumors. Our results support the efficacy of Rlip depletion in suppressing p53 inactivated cancers, and our findings may yield novel methods for prevention or treatment of cancer in patients with HER2 mutations or tumor HER2 expression.

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Cao, Jingyan, Ran Wang, Ning Gao, Minghui Li, Xuyu Tian, Weili Yang, Ying Ruan, et al. "A7RC peptide modified paclitaxel liposomes dually target breast cancer." Biomaterials Science 3, no. 12 (2015): 1545–54. http://dx.doi.org/10.1039/c5bm00161g.

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Omenn, Gilbert S., Anastasia K. Yocum, and Rajasree Menon. "Alternative Splice Variants, a New Class of Protein Cancer Biomarker Candidates: Findings in Pancreatic Cancer and Breast Cancer with Systems Biology Implications." Disease Markers 28, no. 4 (2010): 241–51. http://dx.doi.org/10.1155/2010/705847.

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Alternative splicing plays an important role in protein diversity without increasing genome size. Earlier thought to be uncommon, splicing appears to affect the majority of genes. Alternative splice variants have been detected at the mRNA level in many diseases. We have designed and demonstrated a discovery pipeline for alternative splice variant (ASV) proteins from tandem MS/MS datasets. We created a modified ECgene database with entries from exhaustive three-frame translation of Ensembl transcripts and gene models from ECgene, with periodic updates. The human database has 14 million entries; the mouse database, 10 million entries. We match MS/MS findings against these potential translation products to identify and quantify known and novel ASVs. In this review, we summarize findings and systems biology implications of biomarker candidates from a mouse model of human pancreatic ductal adenocarcinoma [28] and a mouse model of human Her2/neu-induced breast cancer [27]. The same approach is being applied to human tumors, plasma, and cell line studies of other cancers.

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Ko, Jesang, Seung Min Shin, Young Mi Oh, Youn Soo Lee, Zae Yoong Ryoo, Young Han Lee, Doe Sun Na, and Jin Woo Kim. "Transgenic mouse model for breast cancer: induction of breast cancer in novel oncogene HCCR-2 transgenic mice." Oncogene 23, no. 10 (December 22, 2003): 1950–53. http://dx.doi.org/10.1038/sj.onc.1207356.

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Bimonte, Sabrina, Antonio Barbieri, Giuseppe Palma, Domenica Rea, Antonio Luciano, Massimiliano D’Aiuto, Claudio Arra, and Francesco Izzo. "Dissecting the Role of Curcumin in Tumour Growth and Angiogenesis in Mouse Model of Human Breast Cancer." BioMed Research International 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/878134.

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Breast cancer is considered the most common cancer for women worldwide and it is now the second leading cause of cancer-related deaths among females in the world. Since breast cancer is highly resistant to chemotherapy, alternative anticancer strategies have been developed. In particular, many studies have demonstrated that curcumin, a derivative of turmeric, can be used as natural agent in treatment of some types of cancer by playing antiproliferative and antioxidant effects. In our study, we assessed the antitumor activities of curcumin in ER-negative human breast cancer cell line resistant to chemotherapy, MDA.MB231 byin vitroandin vivoexperiments.In vitrodata allowed us to demonstrate that curcumin played a role in regulation of proliferation and apoptosis in MDA.MB231 cells.In vivo, by generation of mouse model of breast cancer, we showed that treatment of curcumin inhibited tumor growth and angiogenesis. Specifically, we showed that curcumin is able to deregulate the expression of cyclin D1, PECAM-1, and p65, which are regulated by NF-κB. Our data demonstrated that curcumin could be used as an adjuvant agent to chemotherapy in treatment of triple negative breast cancer.

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Magna, Melinda, Marc E. Lippman, and Barry I. Hudson. "Abstract B46: Immune characterization of C57BL/6J syngeneic breast cancer mouse models for application in immunotherapy development." Cancer Immunology Research 10, no. 12_Supplement (December 1, 2022): B46. http://dx.doi.org/10.1158/2326-6074.tumimm22-b46.

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Abstract Background: Breast cancer is the second leading cause of cancer-related mortality in women worldwide. While immunotherapy has shown success in various solid tumors, it has been largely ineffective in breast cancer. Critical to establishing effective immunotherapies in breast cancer is the development and better characterization of the tumor immunology of immunocompetent syngeneic models. Here, we describe the molecular and in-depth immunological characterization of three C57BL/6J syngeneic breast cancer mouse models: AT3, Py8119 and E0771 cells. Methods: AT3, Py8119, and E0771 cells were obtained from commercial sources. 5x105 cells were implanted orthotopically in 8 weeks old C57BL/6J female mice. Tumors were isolated from mice and breast cancer subtype classification was performed by immunohistochemical (IHC) staining of estrogen receptor alpha (ERα), progesterone receptor (PR) and Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2/HER2). T cell and myeloid cell infiltration patterns of the tumors were determined by CD3 and CD11b IHC staining respectively. Immunophenotyping of splenic immune cell populations and tumor-infiltrating immune cells was performed with multicolor flow cytometry in all three models. Results: Based on the IHC analysis of the orthotopic murine tumors, E0771 and Py8119 tumors fit the histopathological criteria of triple-negative breast cancer models, while AT3 tumors appear to be a model of the HER2-enriched breast cancer subtype. We show significant differences between the AT3, Py8119 and E0771 models regarding the accumulation of myeloid cells (mMDSC, gMDSC, macrophages, dendritic cells) in the tumor and spleen. Furthermore, analysis of tumor-infiltrating CD4 and CD8 T lymphocytes showed high expression levels of PD-1 in all three models, and varying levels of expression of other immune checkpoint molecules (CTLA4, TIM3, LAG3 and PD-L1) that were model specific. Furthermore, flow cytometry analysis also revealed high levels of PD-L1 expression on all three tumor cell types. Conclusion: In summary, we determined the breast cancer molecular subtype, and described the splenic and intratumoral immune landscape of the AT3, Py8119 and E0771 orthotopic C57BL/6J syngeneic breast cancer mouse models. These data will aid the better design of future tumor immunological studies and provide essential knowledge about these preclinical breast cancer models for use in immunotherapy development. Citation Format: Melinda Magna, Marc E Lippman, Barry I Hudson. Immune characterization of C57BL/6J syngeneic breast cancer mouse models for application in immunotherapy development [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B46.

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Ahn, Tae-Gyu, Byoung-Rai Lee, Eun-Young Choi, Dong Won Kim, and Sei-Jun Han. "Photodynamic therapy for breast cancer in a BALB/c mouse model." Journal of Gynecologic Oncology 23, no. 2 (2012): 115. http://dx.doi.org/10.3802/jgo.2012.23.2.115.

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Gu, Y. H., T. Yamasita, D. J. Choi, H. Yamamoto, T. Matsuo, N. Washino, J. H. Song, and K. M. Kang. "The anticancer effect of plant enzymes on mouse breast cancer model." Advancement in Medicinal Plant Research 6, no. 4 (November 2018): 70–77. http://dx.doi.org/10.30918/ampr.64.18.027.

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BUSS, LINDA A., ANISHAH MANDANI, ELISABETH PHILLIPS, NICOLA J. A. SCOTT, MARGARET J. CURRIE, and GABI U. DACHS. "Characterisation of a Mouse Model of Breast Cancer with Metabolic Syndrome." In Vivo 32, no. 5 (2018): 1071–80. http://dx.doi.org/10.21873/invivo.11348.

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DeVette, Christa, Ismail Can, Atakan Ekiz, Alana Welm, and William H. Hildebrand. "O43 Therapeutic vaccination against breast cancer in a transgenic mouse model." Human Immunology 78 (September 2017): 40. http://dx.doi.org/10.1016/j.humimm.2017.06.049.

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Kuperwasser, Charlotte, Scott Dessain, Benjamin E. Bierbaum, Dan Garnet, Kara Sperandio, Gregory P. Gauvin, Stephen P. Naber, Robert A. Weinberg, and Michael Rosenblatt. "A Mouse Model of Human Breast Cancer Metastasis to Human Bone." Cancer Research 65, no. 14 (July 15, 2005): 6130–38. http://dx.doi.org/10.1158/0008-5472.can-04-1408.

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Journal articles on the topic 'Mouse model and breast cancer'

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