Dissertations / Theses on the topic 'Tumorigenesis'
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Rocchi, Laura <1982>. "mRNAs translation and tumorigenesis." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4363/1/Rocchi_Laura_tesi.pdf.
Full textRocchi, Laura <1982>. "mRNAs translation and tumorigenesis." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4363/.
Full textCripps, Kathryn Jane. "Genetic events in colorectal tumorigenesis." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/27836.
Full textJonkers, Yvonne Margaretha Hendrika. "Molecular alternations during insulinoma tumorigenesis." [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Universiteit Maastricht [host], 2007. http://arno.unimaas.nl/show.cgi?fid=8685.
Full textHobeika, Alice. "Notch1 signaling in mammary tumorigenesis." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110389.
Full textL'activation aberrante des récepteurs Notch a été impliqué dans le cancer du sein. Notre groupe ainsi que quelques autres ont démontré que l'expression d'un transcrit Notch1 muté, codant principalement pour le domaine intracellulaire de Notch1 (Notch1IC) provoque la transformation des cellules en culture et le développement de tumeurs chez les souris transgéniques. Cependant, les mécanismes contribuant à la tumorigénèse induite par Notch1IC demeurent méconnus et la longue période de latence avant l'apparition de tumeurs chez les souris Tg semble indiquer que Notch nécessite la collaboration des mutations secondaires pour engendrer la transformation cellulaire et la formation de tumeurs. Dans le but d'étudier les effets directs en aval de l'expression de Notch1IC, nous avons généré un système d'expression inductible Tet-ON pour Notch1IC dans les cellules épithéliales mammaires Hc11. Dans les lignées cellulaires inductibles établies, l'expression du transgène n'est activée que lors de l'addition de doxycycline (DOX) au milieu de culture. Les cellules inductibles sont capables de former des colonies en agar lorsqu'elles sont induites à la DOX en continu, et elles forment des tumeurs avec métastases aux poumons lorsque transplantées dans des souris traitées à la DOX. Nous avons effectué une analyse de l'expression du génome entier par micropuce dans le but de comparer l'expression des gènes à la suite de l'induction Notch1IC durant 24 heures, à celle de cellules homologues non-induites. 26 gènes ont été identifiés comme étant régulés à la hausse (2 fois et plus) suite à l'expression de Notch1IC, tandis que 5 gènes ont été identifiés comme étant régulés à la baisse. La plupart des gènes ainsi identifiés représentent de nouvelles cibles candidates de Notch1.Parmi ces cibles candidates, l'expression du transcrit pour M-cadhérine (CDH15) a été le plus significativement élevée (19 fois). M-cadhérine, une molécule d'adhésion cellulaire, a été identifiée dans les cellules myogéniques de souris; la protéine est principalement exprimée durant le développement de muscles squelettiques et au cours de la myogenèse secondaire. Dans le muscle squelettique mature, M-cadhérine est principalement détectable dans les cellules satellites. Fait intéressant, un rôle pour M-cadhérine dans les tumeurs d'origine épithéliale n'a pas été précédemment documenté, d'autant plus que M-cadhérine n'a pas été associée à la voie de signalisation Notch.Nous avons d'abord confirmé la surexpression de M-cadhérine par RT-PCR semi-quantitatif dans les cellules Notch1IC-inductibles. In vivo, l'expression de Notch1IC dans les tumeurs mammaires de souris Tg corrélait également avec une forte expression de M-cadhérine. Nous avons également déterminé que la régulation de la transcription de M-cadhérine se produit, au moins en partie, par la voie de signalisation canonique (CSL-dépendante) de Notch1. Par ailleurs, en utilisant des shRNA pour supprimer l'expression de M-cadhérine dans des lignées cellulaires dérivées de tumeurs mammaires provenant de nos souris MMTV/Notch1IC, nous avons pu étudier la fonction de M-cadhérine dans l'oncogénèse induite par Notch1IC. Par le biais d'essais in vitro et in vivo, nous avons démontré que M-cadhérine était requise pour la transformation des cellules MMTV/Notch1IC ainsi que pour leur capacité à former des tumeurs chez la souris. Par la suite, nous avons également confirmé l'expression de M-cadhérine dans plusieurs lignées cellulaires de cancer du sein. Un bref survol de bases de données d'expression génique dans des cancers humain suggère que M-cadhérine serait impliquée dans plusieurs types de cancers, et qu'il y aurait une corrélation entre les niveaux d'expression de M-cadhérine et de Notch1 dans certains cancers du sein.Une meilleure compréhension des mécanismes d'action de M-cadhérine pourrait mener à de nouvelles approches thérapeutiques ciblées pour le traitement des cancers surexprimant Notch1.
Hong, Karen H. (Karen Hsiao-Ying) 1971. "Mouse modifiers of intestinal tumorigenesis." Thesis, Massachusetts Institute of Technology, 2001. http://hdl.handle.net/1721.1/8585.
Full textIncludes bibliographical references.
Colorectal cancer involves a series of molecular alterations as a normal cell progresses to malignancy. A large body of evidence points to the mutation of the APC gene as the pivotal event initiating intestinal tumorigenesis. Apdmin, an induced mutation in mouse homologue of APC, was identified several years ago by Moser et al., providing a genetic model system to study this process. We used the Apdmin system to identify additional genes influencing tumorigenesis. One of these genes,. Mom1 (Modifier of Min-1), involves the effect of genetic background on the Apdmin phenotype. On C57BL/6 (B6), the strain on which Apdmin arose, mice develop approximately 100 tumors. However, B6 X AKR Fl hybrids develop five-fold fewer tumors. Mom1 was identified as the major locus controlling this variation and localized to a 15 cM region on distal mouse chromosome 4 by Dietrich et al. To positionally clone Mom1, Gould et al created a B6.Mom1 AKR congenic strain isolating Mom1 from other AKR resistance factors. Separated from other loci, a single copy of Mom1 AKR reduced tumor number by 50% and two copies produced a 70% reduction. We have used recombinant lines derived from B6.Mom1 AKR to mapMom1 to a 4-cM interval containing one candidate gene, the group IIA secretory phospholipase a2 (sPLA2-IIA). Only tumor prone Mom1 strains, such as B6, contain a mutation in sPLA2-IIA abolishing expression. In order to rigorously measure the effect of sPLA2-IIA on the Apdmin tumor phenotype, we have created and analyzed transgenic lines that restore sPLA2-IIA expression. While we conclude that sPLA2-IIA is indeed protective, tumor number is only reduced by approximately 30%, suggesting that sPLA2-IIA is only part of Mom1. Analysis of additional Moml AKR recombinant strains containing and lacking sPLA2-IIA also implicates a separate distal modifier that accounts for the remaining resistance. To further probe how phospholipases impinge on intestinal cancers, we have studied tumorigen-sis in mice lacking group IV cytosolic phospholipase a2 (cPLA2). Crossing ApcMin into this background produces an 83% reduction in tumor number in ApcMin, cPLA2 -/- homozygotes, suggesting that cPLA2 expression promotes tumorigenesis, most likely via the production of arachidonic acid for downstream eicosanoid synthesis.
by Karen H. Hong.
Ph.D.
Tam, Mandy Chi-Mun. "Genomic analysis of mouse tumorigenesis." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/37454.
Full textIncludes bibliographical references.
The availability of the human and mouse genome sequences has spurred a growing interest in analyzing mouse models of human cancer using genomic techniques. Comparative genomic studies on mouse and human tumors can be valuable in two major ways: in validating mouse models and in identifying genes that are common to mouse and human tumorigenesis. Many analytic tools have emerged in recent years for human genome mining. Some of these tools have been translated to the murine versions. The work in this thesis described the application of two new whole-genome analytic techniques to study mouse tumorigensis: Representational Oligonucleotide Microarray Analysis (ROMA) for tumor DNA copy number asessment and single nucleotide polymorphism (SNP) genotyping using the SNaPshotM system (Applied Biosystems) to detect loss of heterozygosity (LOH) in mouse tumors. The murine version of ROMA was tested on DNA from early-stage KrasGJ2D-derived lung cancers and metastatic retinoblastoma in mice with retinal-specific Rb and p130 deletions. We were interested in identifying the additional genetic lesions that got positively selected during tumorigenesis of these mice.
(cont.) Several recurrent chromosomal copy number gains and losses were observed in the DNA of KrasGJ2D-derived lung tumors. In addition, a focal amplification of the murine N-Myc locus was detected in the metastatic retinoblastomas, demonstrating the capability of ROMA to detect copy number changes at a single-gene resolution. For genome-wide allelotyping, a panel of 147 mouse SNPs were individually validated in 129S4/SvJae vs. C57BL/6J strains and were chosen as markers in the genotyping panel. We worked out a multiplex protocol to genotype the SNPs in an efficient manner. Through this protocol, we generated low-density global LOH maps of lung tumors from mice expressing KrasG12D. LOH that spanned entire chromosomes was seen in a subset of the tumors. A loss of the wild-type p53 allele was also observed in some cases.
by Mandy Chi-Mun Tam.
Ph.D.
Cabrerizo, Granados David 1993. "Endothelial Snail1 in angiogenesis and tumorigenesis." Doctoral thesis, Universitat Pompeu Fabra, 2020. http://hdl.handle.net/10803/670305.
Full textSnail1 es un factor de transcripción con gran relevancia en el desarrollo tumoral, siendo necesario para la transición epitelio-mesénquima y la activación de fibroblastos asociados al cáncer (CAF). En esta tesis, hemos reportado la expresión de Snail1 en células endoteliales de tumor, jugando un papel fundamental en angiogénesis, promoviendo su migración, invasión y tubulogenesis in vitro. Estas funciones están asociadas a la inducción de Snail1 por FGF2 y VEGF-A, que generan un cambio en el perfil de expresión génica en las células endoteliales y modulan su estado de activación. La depleción específica de Snail1 en el endotelio de ratones adultos no supone un cambio fenotípico evidente; sin embargo, sí controla la angiogénesis y la morfología de los vasos en ensayos de plugs de Matrigel. Además, la eliminación específica de Snail1 en el endotelio del modelo murino de tumores de mama espontáneos MMTV-PyMT provoca el retraso en la iniciación de tumores, siendo éstos menos avanzados y con una morfología papilar. Estos efectos in vivo están asociados a la incapacidad de las células endoteliales sin Snail1 de promover una activación completa de fibroblastos in vitro e in vivo, debido a una señalización reducida de las vías de FGF2 y CXCL12; ni de generar una angiogénesis completa in vivo, con neovasos más anchos y menos invasivos. Cambios similares en la aparición de tumores y en su morfología se observaron en ratones MMTV-PyMT pretratados con el antiangiógenico bevacizumab. En muestras humanas de cáncer de mama pudimos recapitular la mayoría de los descubrimientos de los modelos animales usados. En resumen, estos hallazgos establecen un nuevo papel para Snail1 en las células endoteliales, no solo en angiogénesis, sino también en la aparición tumoral, el desarrollo y el fenotipo del tumor.
Andræ, Johanna. "PDGF in cerebellar development and tumorigenesis." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-4987-5/.
Full textBall, Elizabeth Louise. "Molecular mechanisms of human thyroid tumorigenesis." Thesis, Cardiff University, 2008. http://orca.cf.ac.uk/55767/.
Full textFaluyi, Olusola Olusesan. "Cyclooxygenase 2 expression in intestinal tumorigenesis." Thesis, University of Leeds, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275680.
Full textKumar, Madhu S. (Madhu Sudham). "MicroRNAs in cellular transformation and tumorigenesis." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/47879.
Full textVita.
Includes bibliographical references.
MicroRNAs (miRNAs) are a novel class of small (approximately 23 nucleotides long), highly conserved, non-coding RNAs that function by broadly regulating gene expression. In animals, this regulation is achieved via interaction with target messenger RNAs (mRNAs), largely through their imperfect base pairing with the 3' untranslated regions (3' UTRs) of these target transcripts. Through this imperfect base pairing, miRNAs induce a repression of mRNA translation that is frequently coupled to enhanced turnover of the targeted transcript. This miRNA-mediated repression is highly related to that of RNA interference (RNAi), in which small non-coding RNAs exhibit perfect base pairing with target mRNA transcripts, leading to the endonucleolytic cleavage and degradation of these targeted mRNAs. Computational algorithms have been designed to predict putative miRNA binding sites within mRNAs. Using these predictions, it has been suggested that more than half of all mRNAs within mammals are under the control of miRNAs. Some of the earliest discovered miRNAs (characterized by genetic studies in the nematode Caenorhabditis elegans) were found to control the proliferation and differentiation of the cells in which they were expressed. As altered control of proliferation and differentiation frequently manifest in cancer in mammals, it was suggested that miRNAs might contribute to the development of tumorigenesis.
(cont.) In fact, several miRNAs are frequently deleted or amplified in human cancer and miRNA expression profiling studies have shown widespread reductions in steady-state miRNA levels in human cancers relative to normal tissue. These observations have implied a role for miRNAs in tumorigenesis. However, there is a paucity of functional studies demonstrating a role for miRNAs in oncogenic transformation. In the studies described below, we first provide strong evidence for the global loss of miRNAs in human cancers functionally enhancing cellular transformation and tumorigenesis. This enhanced transformation only occurred within tumor cells, suggesting that inhibiting miRNA biogenesis would not be sufficient to induce tumor formation. Moreover, we demonstrate that inhibition of miRNA processing in cancer must be incomplete, as Dicerl, a component of the miRNA processing pathway, suppresses tumorigenesis via haploinsufficiency. Finally, we examine the role of a specific miRNA family, the let-7 family, in the development of non-small cell lung cancer by showing that let-7 can suppress tumorigenesis via inhibition of its targets K-Ras and HMGA2. Taken together, these findings offer promise, not just for understanding the relationship of miRNAs and cancer, but for developing therapeutic agents against the disease.
by Madhu S. Kumar.
Ph.D.
Waters, Catherine. "Insights into Fhit loss-induced tumorigenesis." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1438185414.
Full textRiley, Timothy E. W. "Post-transcriptional regulation of the c-myc proto-oncogene." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257194.
Full textHipp, Nora [Verfasser]. "Mechanisms of MYC-induced tumorigenesis / Nora Hipp." Ulm : Universität Ulm. Fakultät für Naturwissenschaften, 2014. http://d-nb.info/1052062393/34.
Full textTahkola, J. (Jenni). "Collagen XIII in cardiovascular development and tumorigenesis." Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514289569.
Full textYadollahi, Beta. "The Role of Gas3 in Skin Tumorigenesis." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28670.
Full textMajounie, Elisa. "Molecular dissection of neurofibromatosis type 1 tumorigenesis." Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/54088/.
Full textKaidi, Abderrahmane. "The role of hypoxia in colorectal tumorigenesis." Thesis, University of Bristol, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439670.
Full textGraham, T. A. "The expansion of mutant clones in tumorigenesis." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/18761/.
Full textDickinson, Adam. "The role of mitochondrial DNA in tumorigenesis." Thesis, University of Warwick, 2013. http://wrap.warwick.ac.uk/58415/.
Full textKawano(Akitake), Reiko. "Inhibitory role of Gas6 in intestinal tumorigenesis." Kyoto University, 2013. http://hdl.handle.net/2433/180339.
Full textBonner, Allison E. "Organ development and tumorigenesis: a molecular link." The Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1073936508.
Full textCLARK, ADAM MICHAEL. "THE ROLE OF MAP3K8 IN LUNG TUMORIGENESIS." University of Cincinnati / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1077225470.
Full textSilberman, Rebecca Estelle. "Defining the role of aneuploidy throughout tumorigenesis." Thesis, Massachusetts Institute of Technology, 2021. https://hdl.handle.net/1721.1/130665.
Full textCataloged from the official PDF of thesis.
Includes bibliographical references.
Aneuploidy is a state of genome imbalance which alters the copy number of whole chromosomes. While aneuploidy is rare in healthy tissues, it is one of the most common features of cancerous tumors. Studies of aneuploid yeast and aneuploid mammalian cells growing in culture revealed that aneuploidy induces cellular stress and slows proliferation. So it is surprising that aneuploidy is a hallmark of cancer, a disease of cellular over-proliferation and inappropriate cell survival. We sought to elucidate aneuploidy's role in tumorigenesis by defining the factors that affect the prevalence of aneuploid cells in normal, pre-cancerous, and cancerous tissues. First, we investigated whether aneuploid mammalian cells experience fitness defects in vivo. We found that aneuploidy decreases hematopoietic stem cells' fitness and that aneuploid cells are selected against in normal, regenerating tissues in vivo.
However, we also found that aneuploid cells can accumulate in the hematopoietic system when purifying selection is relaxed following bone marrow reconstitution. We then sought to extend our observations to the context of pre-cancerous tissues. We analyzed the prevalence of aneuploidy in the highly tumorigenic, but histologically normal tissues of women harboring heterozygous germline BRCA2 mutations. Using single-cell sequencing, we revealed that breast cells from BRCA2 mutation carriers lack aneuploidy but feature a distinct form of genome imbalance called sub-chromosomal copy number variants (CNVs), even before the initiation of tumorigenesis. We then analyzed the timing with which these two forms of genome imbalance--whole-chromosomal aneuploidy and sub-chromosomal CNVs--arise during tumorigenesis. We found that CNVs are present in the cells of early precursors of multiple cancers, but that whole-chromosomal aneuploidy arises late in tumorigenesis.
Our findings propose that whole-chromosomal aneuploidy reduces cells' fitness in both normal and pre-cancerous tissues, and that aneuploidy is selected against throughout tumorigenesis. This has implications for the role of aneuploidy in cancer, suggesting that aneuploidy does not contribute to early tumorigenesis.
by Rebecca Estelle Silberman.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biology
Choi, Jinkuk. "Telomerase function in epithelial development and tumorigenesis /." May be available electronically:, 2009. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Full textBonner, Allison E. "Organ development and tumorigenesis a molecular link /." Columbus, Ohio : Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1073936508.
Full textTitle from first page of PDF file. Document formatted into pages; contains xviii, 183 p.; also includes graphics (some col.). Includes abstract and vita. Co-advisors: , Ming You and Christoph Plass, Dept. of Medical Microbiology and Immunology. Includes bibliographical references (p. 172-183).
Capristo, Mariantonietta <1981>. "Respiratory chain complex I dysfunction in tumorigenesis." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4798/1/Capristo_Mariantonietta_Tesi.pdf.
Full textCapristo, Mariantonietta <1981>. "Respiratory chain complex I dysfunction in tumorigenesis." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4798/.
Full textTaylor, Clare Petronella Florence. "The use of fluorescence in situ hybridisation techniques in the diagnosis and prognosis of malignancy." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297282.
Full textSandros, Jens. "Salivary gland tumorigenesis a cytogenetic and molecular study /." Göteborg : Faculty of Odontology, University of Göteborg, University of Göteborg, 1989. http://catalog.hathitrust.org/api/volumes/oclc/20361247.html.
Full textHitchcock, Tamara. "The biological role of psoriasin in breast tumorigenesis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ62753.pdf.
Full textWoo, Yong. "Characterizing the Dynamics of Genome Evolution in Tumorigenesis." Fogler Library, University of Maine, 2009. http://www.library.umaine.edu/theses/pdf/WooY2009.pdf.
Full textSegditsas, Stefania. "Mechanisms of intestinal tumorigenesis resulting from APC mutations." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/15923/.
Full textCromer, Michael Kyle. "Exome sequencing uncovers somatic drivers of endocrine tumorigenesis." Thesis, Yale University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3580657.
Full textTumorigenesis of relatively late onset occurring in patients with no family history of cancer syndromes is assumed to be driven by somatic mutations. The advent of high-throughput sequencing allows unbiased probing for genomic aberrations on an unprecedented scale. Somatic mutations, insertions and deletions, and copy number variations are able to be identified by parallel sequencing of tumor DNA and normal DNA from an individual patient. Somatic aberrations identified are classified as either passenger mutations that do not contribute to tumorigenesis or pathogenic driver mutations. Driver mutations are able to be identified due to their recurrence across multiple affected patients at a frequency greater than would be expected by chance.
Tumors occurring in the same tissue and from the same cell type often display diverse phenotypes with distinct mutational signatures. Therefore I applied high-throughput sequencing to probe for somatic mutations in two very specific endocrine tumor types - parathyroid-producing adenomas and insulin-producing adenomas (insulinomas). Prior to this study, neither tumor type had been probed for somatic mutations in a large-scale, unbiased manner. Though a limited number of mutated genes had been identified to play a role in familial and sporadic tumorigenesis in these tumor types, the majority of pathogenesis remained unexplained.
In order to maximize detection of variation in coding regions of the genome, an exome capture array was applied to the DNA prior to sequencing. In both tumor types, exome sequencing was applied to a small number of tumor-normal tissue pairs. Additional targeted sequencing of candidate driver mutations was then performed using Sanger sequencing on larger validation cohorts of tumors.
Exome sequencing revealed few somatic, protein-altering mutations in each tumor type (average <4 per tumor), therefore any recurrent variation was highly probable to be tumorigenic. Exome sequencing of the parathyroid adenomas revealed that four of eight tumors harbored a frameshift deletion or nonsense mutation in MEN1, which was always accompanied by loss of heterozygosity (LOH) of the remaining wild-type allele. No other mutated genes were shared among the eight tumors. One tumor harbored a Y641N missense mutation of the histone methyltransferase EZH2 gene, previously linked to myeloid and lymphoid malignancy formation. Targeted sequencing in an additional 185 parathyroid adenomas revealed somatic MEN1 mutations in a large number of tumors (35%). Furthermore, this targeted sequencing identified an additional parathyroid adenoma that contained the identical, somatic EZH2 mutation that was found by exome sequencing. This confirms the frequent role of LOH of chromosome 11 and MEN1 gene alterations in sporadic parathyroid adenomas and implicates a previously unassociated methyltransferase gene, EZH2, in endocrine tumorigenesis.
Exome sequencing identified an identical somatic, heterozygous mutation in Yin Yang 1 transcription factor (YY1) in two of seven insulinomas. Targeted sequencing of an additional 36 insulinomas revealed twelve more insulinomas that harbored this identical T372R missense mutation in YY1. This mutation occurs at a highly-conserved residue in a highly-conserved zinc finger DNA-binding domain. ChIP-Seq demonstrated that this mutation changes the DNA motif bound by YY1. This altered binding likely drives pathogenesis due to aberrant regulation of genes not regulated by YY1WT. With the goal of identifying differentially-expressed genes in YY1T372R tumors, I performed gene expression analysis on eleven tumors; six that were YY1WT and five that were YY1T372R. This demonstrated that YY1T372R imparts a unique expression signature. Interestingly, several differentially-expressed genes were involved in key pathways regulating insulin secretion, including ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca2+ channel pore-forming subunit), both of which were upregulated in YY1T372R-tumors. Importantly, in vitro studies using the INS-1 rat insulinoma cell line demonstrated that upregulation of each of gene is sufficient to markedly increase insulin secretion. Furthermore, both genes harbored specific YY1T372R binding sites that may account for their significantly altered expression.
Both studies identify novel driver mutations that shed light on the mechanisms of endocrine tumorigenesis. Furthermore, my findings reinforce the notion that common somatic mutations within the exome account for the majority of instances of sporadic tumorigenesis.
O'Bryant, Deon. "Mechanisms of Age-Related Prostate Growth and Tumorigenesis." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2018. http://digitalcommons.auctr.edu/cauetds/138.
Full textCoutermarsh-Ott, Sheryl Lynn. "Investigations into the role of inflammation in tumorigenesis." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/90788.
Full textPh. D.
Mahoney, Emilia. "Molecular Alterations in Bone Development and Bone Tumorigenesis." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1243957525.
Full textStengel, Kristy R. "Modifiers of Ras-driven Tumorigenesis and Therapeutic Response." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1318610225.
Full textVasiliauskas, Juozas. "Hepatocyte Growth Factor-Like protein In prostate tumorigenesis." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1428070127.
Full textGonzalez, Rachel Marie. "Reduced BRCA1 expression in breast and ovarian tumorigenesis /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/6334.
Full textBowen, Timothy J. "Tumor suppressor dysregulation in mouse models of tumorigenesis /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3170247.
Full textMúnera, Jorge O. "Ets2 regulates colonic stem cells and sensitivity to tumorigenesis." Diss., [La Jolla] : University of California, San Diego, 2010. http://wwwlib.umi.com/cr/ucsd/fullcit?p3397225.
Full textTitle from first page of PDF file (viewed March 30, 2010). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 101-108).
Plym, Forshell Tacha Zi. "Examining the role of metabolism in Myc-driven tumorigenesis." Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet), 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-46564.
Full textSaxena, Swati. "Obesity associated colon tumorigenesis: An assessment of tumor phenotype." Thesis, University of Waterloo, 2006. http://hdl.handle.net/10012/2980.
Full textThree major studies were conducted to investigate phenotypical changes in obesity associated tumors. Firstly, characteristics of the TNF-alpha resistant phenotype were preliminarily assessed by evaluating the effects of exogenous TNF-alpha treatment to HT-29 cells. Elevated levels of NF-kB in response to exogenous TNF-alpha gave an indication that this pathway is critical for cell survival. Furthermore, upregulation of TNF-alpha receptor 2 (TNFR2) suggested another strategy by which the cells were utilizing exogenous TNF-alpha for a survival advantage. Inhibition of NF-kB via St. John?s Wort treatment demonstrated that HT-29 cells may be sensitized towards TNF-alpha mediated cytotoxicity.
Zucker obese (Zk-Ob), Zucker lean (Zk-Ln), and Sprague Dawley (SD) animal models were used to assess tumor phenotype in vivo. Remarkable physiological differences between genotypes were observed. Zk-Ob rats had significantly higher body and organ weights as well as plasma TNF- alpha, insulin, leptin, and oxidative markers than Zk-Ln and SD animals. Tumor incidence and multiplicity were also notably higher in Zk-Ob rats. Protein analyses demonstrated increased levels of TNF-alpha, TNFR2, NF-kB, IkB kinase beta (IKKbeta), insulin receptor (IR), insulin like growth factor-I-receptor (IGF-IR), and mitogen activated protein kinase (MAPK) in Zk-Ob tumors than Zk-Ln counterparts. In all groups, tumors generally had higher protein expression than surrounding, normal appearing colonic mucosa. It is well known that these molecules are involved in signaling pathways that influence and co-operate with each other in rendering growth autonomy to tumor tissue.
A higher number of lesions in the distal than proximal colon in Zk-Ob rats was observed, supporting the emerging concept that genotype/physiological state of the host affects development and distribution of tumors. Thus, a third study was conducted to explore differences between distal and proximal tumor phenotype. Results demonstrated that expression of TNFR2, NF-kB, IR, IGF-IR, and MAPK p44 were significantly higher in distal than proximal tumors. This observation suggested that development of tumors in different regions of the colon varied under the same physiological conditions. Moreover, phenotype of distal tumors appeared to be upregulating survival pathways in comparison to proximal lesions, possibly explaining the higher tumor incidence in the distal colon.
Research documented in this thesis supported the hypothesis that the physiological status of the host intricately affects tumor phenotype. In particular, the TNF-alpha resistant phenotype was most prominent in Zk-Ob tumors, and appeared to be associated with upregulation of multiple signaling pathways cooperating towards tumorigenesis.
Chen, Changfeng. "Retinoic acid receptors and mouse epidermal tumorigenesis and development." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84492.
Full textProgressive loss of RARs is associated with skin carcinogenesis both in human and animals. Despite such observations, the biological significance of RAR loss in skin carcinogenesis has not yet been clarified. To this end, we established keratinocyte cell lines deficient in RARalpha, RARgamma, or both and employed a well-established tumorigenesis model to investigate whether loss of RARs is causally related to skin tumorigenesis. We found that RARgamma is the major RAR subtype mediating the growth and AP-1 inhibitory effects of RA on keratinocytes in vitro. Consistent with this observation, loss of RARgamma, but not RARalpha, predisposed keratinocytes to tumor formation, suggesting that RARgamma may act as a tumor suppressor. Reconstitution of RARs in the RARalphagamma-/- keratinocytes inhibited their tumorigenic potential, further proving that RARs have tumor suppressive effects.
As expected, expression of dnRARalpha resulted in profound epidermal defects. Intriguingly, dnRAalphaDBD caused a virtually identical skin phenotype, suggesting that dnRARalpha acts to affect epidermal development via a DNA-binding-independent mechanism. The epidermal phenotype of these transgenic mice is reminiscent of that seen in the p63-/- mice, and p63 expression was indeed significantly reduced in the epidermis expressing dnRARalpha or dnRARalphaDBD, suggesting that downregulation of p63 by dnRARalpha may be attributable to the epidermal phenotypes associated with the transgenic mice. These observations also suggest that DNA-binding is not required for dnRARalpha to attenuate p63 expression in the epidermis. Consistent with these observations, I also found that p63 is indeed not a RAR-target, as no overt changes in p63 expression were observed in the RARalphagamma-/- epidermis, which appeared normal. (Abstract shortened by UMI.)
He, Zhiheng 1971. "Functional characterization of progranulin in wound healing and tumorigenesis." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37898.
Full textMoore, Amy Elizabeth. "The role of HGF/Met signalling in colorectal tumorigenesis." Thesis, University of Bristol, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.544331.
Full textZhao, Fung, and 趙楓. "Role of FOXM1 in ovarian cancer tumorigenesis and chemoresistance." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/211053.
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Pathology
Doctoral
Doctor of Philosophy
Mao, Jian-Hua. "Stochastic modelling of tumorigenesis in p53 deficient transgenic mice." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286124.
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