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Kahli, Malik. "Implication des protéines HMGA et HMGA2 dans les changements du programme de réplication au cours de la sénescence cellulaire". Thesis, Montpellier 2, 2011. http://www.theses.fr/2011MON20059/document.
Pełny tekst źródłaSenescence, considered as an irreversible cell cycle arrest, is characterized by dramatic changes in genes expression and chromatin organisation forming dense heterochromatic foci (SAHF). These changes are concomitant to a progressive decline of the capactity to replicate the genome. My PhD topic was to investigate whether the chromatin changes induced by SAHF formation could influence the replication program and modify the origin distribution along the genome at replicative senescence. We first compared the origin distribution of proliferative and pre-senescent primary fibroblasts by DNA molecular combing. Then, we mapped the origins positions in whole human genome by using the nascent strand purification assay coupled to deep sequencing.As HMGA1 and HMGA2 proteins are essential to induce SAHF formation, we designed inducible cell lines wich overexpress these proteins, triggering premature senescence. We made the same type of experiments in these cell lines in order to investigate the implication of these proteins on the changes of the replication program we observed during senescence
Saada-Bouzid, Esma. "Étude génomique et fonctionnelle de la dérégulation du gène HMGA2 dans les tumeurs adipocytaires". Thesis, Nice, 2015. http://www.theses.fr/2015NICE4000/document.
Pełny tekst źródłaBenign adipocytic tumors (AT) are mainly represented by lipomas whereas most malignant AT are Atypical Lipomatous Tumors/Well-differentiated liposarcomas (ALT/WDLPS) and dedifferentiated liposarcomas (DDLPS). HMGA2 gene (High Mobility Group A2) is rearranged in some lipomas and amplified in ALT/WDLPS and DDLPS. Thus, we hypothesized that HMGA2 played a fundamental role in benign and malignant AT genesis. In favor of this hypothesis, we observed a constant overexpression of HMGA2 in amplified ALT/WDLPS and DDLPS, and in rearranged lipomas. In a case of lipomatosis, that is a pathological proliferation of the adipocytic tissu without rearrrangement of HMGA2, the overexpression of HMGA2 was asssociated with an inhibition of the expression of several let-7 microRNAs. However, we did not find a leading role of let-7 microRNAs in the deregulation of HMGA2 expression in AT. We also studied partner fusion genes of HMGA2 in lipomas and have specifically identified a new fusion involving PPAP2B (Phosphatidic Acid Phosphatase type 2B) which is located in 1p32. We also confirmed the role of NFIB gene (9p22) in lipomas. Finally, we have established prognostic correlations in a series of 116 ALT/WDLPS and DDLPS: HMGA2 amplification was associated with ALT/WDLPS histotype and a longer survival whereas respective CDK4 and JUN amplification were associated with DDLPS and shorter survival. Thus, our data support the hypothesis of an early and major role of HMGA2 in the genesis well differentiated AT
Wei, Linxuan, Xiaolin Liu, Wenjing Zhang, Yuyan Wei, Yingwei Li, Qing Zhang, Ruifen Dong i in. "Overexpression and oncogenic function of HMGA2 in endometrial serous carcinogenesis". E-CENTURY PUBLISHING CORP, 2016. http://hdl.handle.net/10150/614759.
Pełny tekst źródłaHawsawi, Ohuod. "Role of High Mobility Group A2 (HMGA2) in Prostate Cancer". DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2019. http://digitalcommons.auctr.edu/cauetds/184.
Pełny tekst źródłaAnnewanter, Franka Maria [Verfasser]. "Expression von TRAIL-Rezeptoren und HMGA2 im duktalen Pankreasadenokarzinom / Franka Maria Annewanter". Kiel : Universitätsbibliothek Kiel, 2014. http://d-nb.info/1064306101/34.
Pełny tekst źródłaNatarajan, Suchitra. "Roles of high mobility group AT-hook protein 2 (HMGA2) in human cancers". Elsevier, 2013. http://hdl.handle.net/1993/31092.
Pełny tekst źródłaFebruary 2016
Saada-Bouzid, Esma. "Étude génomique et fonctionnelle de la dérégulation du gène HMGA2 dans les tumeurs adipocytaires". Electronic Thesis or Diss., Nice, 2015. http://www.theses.fr/2015NICE4000.
Pełny tekst źródłaBenign adipocytic tumors (AT) are mainly represented by lipomas whereas most malignant AT are Atypical Lipomatous Tumors/Well-differentiated liposarcomas (ALT/WDLPS) and dedifferentiated liposarcomas (DDLPS). HMGA2 gene (High Mobility Group A2) is rearranged in some lipomas and amplified in ALT/WDLPS and DDLPS. Thus, we hypothesized that HMGA2 played a fundamental role in benign and malignant AT genesis. In favor of this hypothesis, we observed a constant overexpression of HMGA2 in amplified ALT/WDLPS and DDLPS, and in rearranged lipomas. In a case of lipomatosis, that is a pathological proliferation of the adipocytic tissu without rearrrangement of HMGA2, the overexpression of HMGA2 was asssociated with an inhibition of the expression of several let-7 microRNAs. However, we did not find a leading role of let-7 microRNAs in the deregulation of HMGA2 expression in AT. We also studied partner fusion genes of HMGA2 in lipomas and have specifically identified a new fusion involving PPAP2B (Phosphatidic Acid Phosphatase type 2B) which is located in 1p32. We also confirmed the role of NFIB gene (9p22) in lipomas. Finally, we have established prognostic correlations in a series of 116 ALT/WDLPS and DDLPS: HMGA2 amplification was associated with ALT/WDLPS histotype and a longer survival whereas respective CDK4 and JUN amplification were associated with DDLPS and shorter survival. Thus, our data support the hypothesis of an early and major role of HMGA2 in the genesis well differentiated AT
INGRAHAM, SUSAN ELIZABETH. "THE BALANCED, RECIPROCAL TRANSLOCATION OF CHROMOSOMAL SUBBANDS 12q15 AND 14q24 AND ALTERED GENE EXPRESSION IN UTERINE LEIOMYOMA". University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1029433658.
Pełny tekst źródłaAndrieux, Joris. "Anomalies cytogénétiques et moléculaires des myélofibroses avec métaplasie myéloi͏̈de : dérégulation et hyperexpression du gène HMGA2". Lille 2, 2003. http://www.theses.fr/2003LIL2MT21.
Pełny tekst źródłaTan, E.-Jean. "Transcriptional and Epigenetic Regulation of Epithelial-Mesenchymal Transition". Doctoral thesis, Uppsala universitet, Ludwiginstitutet för cancerforskning, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-206120.
Pełny tekst źródłaOliveira, Mateos Cristina. "Epigenetic regulation mediated by antisense non-coding RNAs and its impact on oncogenic pathways: the HMGA2/RPSAP52 locus". Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/669259.
Pełny tekst źródłaLa gran mayoría del genoma humano se transcribe, dando lugar en muchos casos a RNAs no codificantes. Los transcritos antisentido son uno de los tipos más abundantes de RNAs no codificantes largos y muchos poseen importantes funciones en la regulación de los genes cercanos. Este es el caso de RPSAP52, transcrito antisentido del gen codificante HMGA2. La expresión de ambos genes es elevada en varios cánceres humanos y correlaciona positivamente como consecuencia de la regulación que RPSAP52 ejerce sobre HMGA2. RPSAP52 forma un R-loop en la región promotora de los dos genes, lo que modifica la conformación de la cromatina y favorece la transcripción de HMGA2. RPSAP52 desempeña funciones adicionales en el citoplasma gracias a su unión a la proteína IGF2BP2, cuya transcripción es regulada por HMGA2. IGF2BP2 promueve la traducción de genes relacionados con importantes rutas proliferativas, y su interacción con RPSAP52 afecta su unión a algunos RNAs mensajeros, así como su reclutamiento a polisomas. En este trabajo demostramos que LIN28B, uno de los principales reguladores negativos de la maduración del miRNA let-7, es uno de sus targets. De este modo, RPSAP52 aumenta la traducción de LIN28B y reduce los niveles del supresor tumoral let-7. La regulación mediada por RPSAP52 tiene un importante impacto en rutas génicas relacionadas con el cáncer. Su depleción afecta negativamente las características tumorigénicas de las células in vitro y disminuye la progresión tumoral in vivo. Además, RPSAP52 puede ser considerado como un biomarcador en sarcomas, ya que sus altos niveles se asocian a un peor pronóstico. En resumen, el presente trabajo propone un modelo regulador mediado por RPSAP52 con dos niveles diferentes de acción. Este transcrito antisentido promueve la activación transcripcional de HMGA2 y, a su vez, regula la función de la proteína IGF2BP2. Dado que HMGA2 e IGF2BP2 están en la misma vía proliferativa, RPSAP52 refuerza la función de HMGA2 tanto sobre IGF2BP2 como sobre sus efectores posteriores, lo que afecta la progresión del cáncer. Debido a los importantes roles desempeñados por RPSAP52 y a sus propiedades oncogénicas, podría ser una potencial diana terapéutica para el desarrollo de nuevos tratamientos contra el cáncer.
Singh, Indrabahadur [Verfasser]. "HMGA2-mediated epigenetic regulation of Gata6 controls epithelial canonical WNT signaling during lung development and homeostasis / Indrabahadur Singh". Gießen : Universitätsbibliothek, 2015. http://d-nb.info/107435513X/34.
Pełny tekst źródłaSchwarm, Frank [Verfasser]. "Expressionsanalyse und klinische Bedeutung des High-mobility Group AT-hook 2 Antigens (HMGA2) in humanen Glioblastomen / Frank Patrick Schwarm". Gießen : Universitätsbibliothek, 2018. http://d-nb.info/1155405579/34.
Pełny tekst źródłaSchwarm, Frank Patrick [Verfasser]. "Expressionsanalyse und klinische Bedeutung des High-mobility Group AT-hook 2 Antigens (HMGA2) in humanen Glioblastomen / Frank Patrick Schwarm". Gießen : Universitätsbibliothek, 2018. http://d-nb.info/1155405579/34.
Pełny tekst źródłaOhlmann, Anne Katharina [Verfasser]. "Untersuchung von HMGA2 als prognostischer Faktor bei Plattenepithelkarzinomen der Mundschleimhaut insbesondere im Vergleich zu anderen prognostischen Markern / Anne Katharina Ohlmann". Kiel : Universitätsbibliothek Kiel, 2017. http://d-nb.info/1147380120/34.
Pełny tekst źródłaAguiar, Tamiris Sayuri. "Caracterização de variação no número de cópias (CNV) no gene HMGA2 associado com tamanho de prepúcio em bovinos nelore (Bos indicus) /". Jaboticabal, 2018. http://hdl.handle.net/11449/154763.
Pełny tekst źródłaBanca: Silvana de Cássia Paulan
Banca: Flávia Lombardi Lopes
Resumo: O gene High Mobility Group AT-hook2 (HMGA2) apresentou fortes evidências de estar associado com o tamanho de umbigo em bovinos da raça Nelore através da análises de associação genômica ampla (GWAS). Diversos relatos de associação desse gene a fenótipos do âmbito da morfologia corporal existem para diferentes espécies, tais como altura em humanos, cães e equinos, e tamanho da orelha em suínos. Descobertas recentes demonstraram que o gene HMGA2 está associado avia metabólica de grande importância fisiológica e biológica que tem como um dos principais fatores o PLAG1 (Pleomorphic adenoma gene1), que está associado ao fator de crescimento semelhante à insulina 2 (IGF2), importante regulador do crescimento e da reprodução em bovinos. No presente trabalho, foi descritaa identificação e caracterização de variação no número de cópias (CNV) cromossomo 5 do cromossomo bovino, na região do gene HMGA2 que apresenta associação a característica de tamanho de umbigo. Análises da sequência completa do genoma de indivíduos Bos taurus e Bos indicus foram empregadas para caracterizar o CNV, sendo sua validação realizada através de PCR quantitativo (qPCR). Além disso, os resultados foram comparados com dados de sequência de animais africanos B. indicus evidenciando a origem zebuína do CNV.
Abstract: The High Mobility Group AT-hook 2 (HMGA2) gene presented strong evidence of being associated with navel size in Nellore cattle through genome association analysis (GWAS). Several reports of association of this gene with phenotypes in the scope of body morphology exist for different species, such as height in humans, dogs and horses, and ear size in swine. Recent discoveries have shown that the HMGA2 gene is associated with a metabolic pathway of great physiological and biological importance that has as one of its main factors PLAG1 (Pleomorphic adenoma gene 1), which is associated with insulin-like growth factor 2 (IGF2), important regulator of growth and reproduction in cattle. In the present work, the identification and characterization of copy number variation (CNV) on chromosome 5 of the bovine chromosome in the region of the HMGA2 gene that has association with the navel size trait was described. Genome sequence analysis of Bos taurus and Bos indicus individuals was used to characterize the CNV, and its validation was performed using quantitative PCR (qPCR). In addition, the results were compared with sequence data from a African B.indicus animals evidencing the indicine origin of the CNV.
Mestre
Mello, Julia Bette Homem de [UNESP]. "Caracterização de mutações no gene MED12, dos miRNAS mapeados em 7q22 e dos candidatos a regulação do gene HMGA2 em leiomiomas uterinos". Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/92717.
Pełny tekst źródłaLeiomiomas uterinos (LU) são tumores benignos de origem mesenquimal frequentes sendo considerados um problema de saúde pública. A desregulação de fatores de crescimento e microRNAs, encurtamento dos telomeros, produção excessiva e desorganizada de matriz extracelular, perda de heterozigose e alterações cromossômicas recorrentes (como deleção em 7q22 e rearranjo cromossômico em 12q15) contribuem para o crescimento dos LU. Uma parcela significativa destes tumores apresenta mutação no gene MEDI2. O presente estudo teve como objetivo avaliar: a presença da mutação no MEDI2; o nível de expressão do HMGA2 e seus miRNAs preditos (let-7a, miR-26a, miR-26b); o nível de expressão do, cluster de miRNAs mapeado em 7q22 (miR-25, miR-93 e miR- 106b) e a expressão dos genes BRCAI, FANCA e seus miRNAs preditos. Foram avaliados 85 LU e 34 amostras de miométrio adjacentes obtidos de 54 pacientes submetidos à histerectomia. A análise de expressão por RT-qPCR foi realizada para os miR-let7a, miR-25, miR-93, miR-106b, miR-21, miR-26a, miR-26b, miR-197 e miR- 143, utilizando RNU44 , RNU48 e U47 como endógenos. Foi também avaliada a expressão dos genes HMGA2, BRCAI e FANCA sendo utilizados como controles endógenos RPLPO e GUSB. A mutação no MED12 foi encontrada em 50% (42/85) das amostras. Foi observado um aumento significativo (p<0,001) dos níveis de expressão do HMGA2 nos LU comparados ao miométrio adjacente, inclusive nas amostras com presença da mutação em MEDI2. Estes dados sugerem que o aumento de expressão do HMGA2 e a mutação em MEDI2 podem coexistir nestes tumores. Os miRNAs preditos para regular o HMGA2 apresentaram diminuição dos níveis de expressão: let-7a (p
Busch, Bianca [Verfasser], Stefan [Akademischer Betreuer] Hüttelmaier, Guido [Akademischer Betreuer] Posern i Gunter [Akademischer Betreuer] Meister. "Charakterisierung des miR-let-7-abhängigen onkogenen Netzwerks von IGF2BP1-LIN28B-HMGA2 in Ovarialkarzinomzellen / Bianca Busch ; Stefan Hüttelmaier, Guido Posern, Gunter Meister". Halle, 2016. http://d-nb.info/1116952165/34.
Pełny tekst źródłaMello, Julia Bette Homem de. "Caracterização de mutações no gene MED12, dos miRNAS mapeados em 7q22 e dos candidatos a regulação do gene HMGA2 em leiomiomas uterinos /". Botucatu, 2013. http://hdl.handle.net/11449/92717.
Pełny tekst źródłaBanca: Rafael Malagoli Rocha
Banca: Robson Francisco Carvalho
Resumo: Leiomiomas uterinos (LU) são tumores benignos de origem mesenquimal frequentes sendo considerados um problema de saúde pública. A desregulação de fatores de crescimento e microRNAs, encurtamento dos telomeros, produção excessiva e desorganizada de matriz extracelular, perda de heterozigose e alterações cromossômicas recorrentes (como deleção em 7q22 e rearranjo cromossômico em 12q15) contribuem para o crescimento dos LU. Uma parcela significativa destes tumores apresenta mutação no gene MEDI2. O presente estudo teve como objetivo avaliar: a presença da mutação no MEDI2; o nível de expressão do HMGA2 e seus miRNAs preditos (let-7a, miR-26a, miR-26b); o nível de expressão do, cluster de miRNAs mapeado em 7q22 (miR-25, miR-93 e miR- 106b) e a expressão dos genes BRCAI, FANCA e seus miRNAs preditos. Foram avaliados 85 LU e 34 amostras de miométrio adjacentes obtidos de 54 pacientes submetidos à histerectomia. A análise de expressão por RT-qPCR foi realizada para os miR-let7a, miR-25, miR-93, miR-106b, miR-21, miR-26a, miR-26b, miR-197 e miR- 143, utilizando RNU44 , RNU48 e U47 como endógenos. Foi também avaliada a expressão dos genes HMGA2, BRCAI e FANCA sendo utilizados como controles endógenos RPLPO e GUSB. A mutação no MED12 foi encontrada em 50% (42/85) das amostras. Foi observado um aumento significativo (p<0,001) dos níveis de expressão do HMGA2 nos LU comparados ao miométrio adjacente, inclusive nas amostras com presença da mutação em MEDI2. Estes dados sugerem que o aumento de expressão do HMGA2 e a mutação em MEDI2 podem coexistir nestes tumores. Os miRNAs preditos para regular o HMGA2 apresentaram diminuição dos níveis de expressão: let-7a (p
Mestre
Winter, Nina [Verfasser], Jörn [Akademischer Betreuer] Bullerdiek i Burkhard [Akademischer Betreuer] Helmke. "Nachweis der Expression von HMGB1 und HMGA2 zur Anwendung in der Tumor- und Pränataldiagnostik / Nina Winter. Gutachter: Jörn Bullerdiek ; Burkhard Helmke. Betreuer: Jörn Bullerdiek". Bremen : Staats- und Universitätsbibliothek Bremen, 2012. http://d-nb.info/1071993445/34.
Pełny tekst źródłaThies, Helge Wilhelm [Verfasser], Jörn [Akademischer Betreuer] Bullerdiek i Andreas [Akademischer Betreuer] Dotzauer. "Untersuchung zur Rolle von HMGA2 im Fettgewebe: Mechanismen des Turnovers und der Hyperplasie / Helge Wilhelm Thies. Gutachter: Jörn Bullerdiek ; Andreas Dotzauer. Betreuer: Jörn Bullerdiek". Bremen : Staats- und Universitätsbibliothek Bremen, 2014. http://d-nb.info/107215840X/34.
Pełny tekst źródłaMüller, Marietta Henrike [Verfasser], Jörn [Akademischer Betreuer] Bullerdiek i Andreas [Akademischer Betreuer] Dotzauer. "Dysregulation of the high mobility group AT-hook 2 (HMGA2) gene in human tumours / Marietta Henrike Müller. Gutachter: Jörn Bullerdiek ; Andreas Dotzauer. Betreuer: Jörn Bullerdiek". Bremen : Staats- und Universitätsbibliothek Bremen, 2014. http://d-nb.info/1072226219/34.
Pełny tekst źródłaWeihrauch, Marc-Andreas Günter. "Butyrat moduliert die Expression der Nicht-Histon-Proteine HMGA1, HMGN1 und HMGN2 in humanen Adenokarzinomzellen des Kolons und des Magens". [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971750556.
Pełny tekst źródłaCaron, Leslie. "Rôle de la voie ERK et du facteur de transcripion HMGA2 dans la différenciation des cellules souches embryonnaires de souris : établissement du système d'expression inductible Lacl-IPTG dans ces cellules". Nice, 2004. http://www.theses.fr/2004NICE4068.
Pełny tekst źródłaWe investigated the role of the HMGA2 transcription factor during mouse embryonic stem cells differentiation (ES cells). ES cells overexpressing either wild-type (HMGA2wt) or truncated (HMGA2/T) form of HMGA2 were analysed for their capacities to differentiate into a variety of lineage. Following differentiation, as opposed to control cells and HMGA2wt ES cells, overexpressing HMGA2/T ES cells massively formed contractile myotubes and highly expressed the muscle Myosin Heavy Chain marker. Interestingly, in experimental conditions inhibitory for myogenesis, we observed a strong expression of MyoD and myogenin in HMGA2/T cells. By contrast, commitment into adipocyte, neuron and cadiomyocyte lineages was not affected. Finally, teratocarcinomas induced by HMGA2/T ES cell lines presented numerous skeletal muscle-differentiated tissues that were not observed in wt HMGA2 or control tumors. Our results reveal a novel function of the oncogenic form of HMGA2 in skeletal muscle differentiation. Control of mammalian gene promoters by the bacterial LacI repressor provides inducible regulation and dose-response levels of expression by the lactose analog IPTG. We show that insertion of LacI binding sites in the b-actin promoter confers an efficient IPTG-regulatable expression of reporter genes in ES cells expressing LacI. We established ES cell lines stably expressing GFP under inducible control and found that this regulatable expression was maintained throughout the differentiation process. Importantly, GFP induction by IPTG was observed in individual well-differentiated cardiomyocytes and neurons. This inducible system will be used to study HMGA2 during ES cells differentiation
Sneesby, Kyra, i n/a. "Gene Expression in Embryonic Chick Heart Development". Griffith University. School of Biomolecular and Biomedical Science, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20030924.153514.
Pełny tekst źródłaSneesby, Kyra. "Gene Expression in Embryonic Chick Heart Development". Thesis, Griffith University, 2003. http://hdl.handle.net/10072/367647.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Full Text
Kloth, Lars-Gerrit [Verfasser], Jörn [Akademischer Betreuer] Bullerdiek i Andreas [Akademischer Betreuer] Dotzauer. "Quantitative analysis of thyroid adenoma associated (THADA) and high-mobility group AT-hook 2 (HMGA2) in dedifferentiated and extra-embryonic human tissues / Lars-Gerrit Kloth. Betreuer: Jörn Bullerdiek. Gutachter: Jörn Bullerdiek ; Andreas Dotzauer". Bremen : Staats- und Universitätsbibliothek Bremen, 2015. http://d-nb.info/1077864280/34.
Pełny tekst źródłaLamichhaney, Sangeet. "The genetic basis for adaptation in natural populations". Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-279969.
Pełny tekst źródłaROS, GLORIA. "ROLE OF HMGA1 IN BREAST CANCER AGGRESSIVENESS". Doctoral thesis, Università degli Studi di Trieste, 2016. http://hdl.handle.net/11368/2908068.
Pełny tekst źródłaBeitzel, Brett F. "The role of HMGA proteins in retroviral integration /". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3099924.
Pełny tekst źródłaArnoldo, Laura. "HMGA1 proteins regulate gene expression by modulating histone H3 phosphorylation". Doctoral thesis, Università degli studi di Trieste, 2014. http://hdl.handle.net/10077/10112.
Pełny tekst źródłaHMGA1 is an oncogene encoding for an architectural transcription factor that affects fundamental cell processes, leading to neoplastic transformation. The two main mechanisms by which HMGA1 protein is known to be involved in cancer concern the regulation of gene expression by altering DNA structure and interacting with a conspicuous number of transcription factors. Here we provide evidence of an additional level of gene expression regulation exploited by HMGA1 to exert its oncogenic activity. Starting from protein-protein interaction data showing that HMGA1 interacts with histones, we show that HMGA1 regulates gene expression by affecting the epigenetic status of cancer cells. In particular, it modulates the signalling cascade mediated by the RAS/RAF/MEKK/ERK/RSK2 pathway regulating the levels of histone H3 phosphorylation at Serine 10 and Serine 28. We demonstrate that the down-regulation of these two H3 post-translational modifications by HMGA1 silencing and by inhibitors of the RAS/RAF/MEKK/ERK pathway is linked to cell migration decrease and morphological changes resembling the mesenchymal to epithelial transition.
HMGA1 è un oncogene codificante per un fattore trascrizionale architetturale che influenza fondamentali processi cellulari, portando alla trasformazione neoplastica. I due principali meccanismi tramite cui la proteina HMGA1 è nota essere coinvolta nel cancro riguardano la regolazione dell’espressione genica tramite l’alterazione della struttura del DNA e l’interazione con un cospicuo numero di fattori di trascrizione. Qui forniamo la prova di un addizionale livello di regolazione dell’espressione genica sfruttato da HMGA1 per esercitare la sua attività oncogenica. Partendo da dati d’interazione proteina-proteina che mostrano che HMGA1 interagisce con gli istoni, mostriamo che HMGA1 regola l’espressione genica influenzando lo stato epigenetico delle cellule cancerose. In particolare, essa modula la cascata di segnalazione mediata dalla via di RAS/RAF/MEKK/ERK/RSK2 regolando i livelli di fosforilazione dell’istone H3 sulla Serina 10 e sulla Serina 28. Noi dimostriamo che la down-regolazione di queste due modificazioni post-traduzionali di H3 tramite il silenziamento di HMGA1 e l’utilizzo di inibitori della via di RAS/RAF/MEKK/ERK/RSK2 è correlata alla diminuzione della migrazione cellulare e a cambiamenti morfologici che ricordano la transizione mesenchimo-epiteliale.
XXV Ciclo
1983
Eren, Elif. "HMA2. A Transmembrane Zn2+ Transporting ATPase from Arabidopsis thaliana". Worcester, Mass. : Worcester Polytechnic Institute, 2007. http://www.wpi.edu/Pubs/ETD/Available/etd-010507-150007/.
Pełny tekst źródłaPellarin, Ilenia. "HMGA PROTEINS IN EPITHELIAL-MESENCHYMAL TRANSITION AND TUMOUR PROGRESSION". Doctoral thesis, Università degli studi di Trieste, 2014. http://hdl.handle.net/10077/10117.
Pełny tekst źródłaHigh Mobility Group A (HMGA1a, HMGA1b and HMGA2) proteins are architectural nuclear factors, physiological expressed during embryonic development and re-expressed at high levels following neoplastic transformation, playing essential functions in both these processes thanks to their particular plasticity and consequently multifunctionality. HMGA are involved in a wide number of cellular processes, including Epithelial-Mesenchymal transition (EMT), a biologic developmental process characterized by the conversion of epithelial cells to motile mesenchymal ones, with increased capacity of migration and invasion. EMT plays a key role during the progression of different tumours, including breast cancer and also HMGA have been linked to these processes in the acquisition of tumourigenic features. Consequently taking advantage of different breast cancer cell lines to recreate an "EMT model" we have investigated the role of HMGA proteins in EMT and breast carcinoma. We have developed a cellular model, stable for the overexpression of HMGA1 using the human breast cancer cell line MCF7. We have explored different aspects of tumourigenesis, performing transwell migration and invasion assays, demonstrating that cells with high levels of HMGA1 migrate and invade at a higher and significant level in comparison to control cells. Moreover this data was also confirmed with the development of an inducible cell line for HMGA1 overexpression. Therefore we have examined the expression status of different genes, including several specific EMT markers at mRNA level with Real Time PCR, observing a pre-malignant change towards mesenchymal status. We have investigated the response after DNA damage induced by doxorubicin drug, by colony formation assay, demonstrating that HMGA1 overexpressing cells confer a survival advantage to the cells, being able to survive and form a significant higher number of colonies in respect to control cells. Therefore to study deeper the role of HMGA in EMT, we have developed other two cellular systems, a human cellular model of EMT in MDA-MB-468 human breast carcinoma cells treated with Epidermal Growth Factor (EGF) and the well known EMT model, elicited by Transforming Growth Factor-β (TGF-β) in murine mammary epithelial NMuMG cells, in which HMGA2 is functionally determinant. We have demonstrated by Real Time PCR of EMT markers, Western Blot analyses and immunofluorescence the effective reliability of these cellular models, confirmed also by a dramatic change in morphology of treated cells, towards a mesenchymal phenotype. Concluding we have interestingly observed that overexpression of HMGA1 could confer some tumourigenic features (i.e. migration, invasion) and survival advantage to the cells in the MCF7 model after a cellular DNA damage induction; therefore we have different suggestions that HMGA are involved in EMT in other different cellular models.
Le proteine HMGA (HMGA1a, HMGA1b e HMGA2), definite come fattori architetturali della cromatina, sono fisiologicamente espresse ad alti livelli nel corso dello sviluppo embrionale diminuendo gradualmente la loro espressione nel corso del differenziamento. Sono coinvolte, oltre all'aspetto fisiologico, anche in diverse condizioni patologiche, essendo ad esempio ri-espresse ad alti livelli nel corso della trasformazione neoplastica, esercitando funzioni essenziali grazie alla loro alta plasticità, alle peculiari caratteristiche biochimiche e conseguente multifunzionalità. Le proteine HMGA utilizzano diversi meccanismi per esercitare la loro funzione nell'acquisire capacità trasformanti, inclusa la transizione epitelio-mesenchimale. Questo processo biologico, primariamente identificato come fattore chiave dello sviluppo embrionale, è risultato di essere di fondamentale importanza anche nella trasformazione tumorale. Mediante questo meccanismo una cellula epiteliale, mediante molteplici cambiamenti genetici e biochimici acquisisce caratteristiche tipiche di uno "stato mesenchimale", caratterizzato ad esempio da un'aumentata capacità invasiva e migratoria. La transizione epitelio-mesenchimale esercita un ruolo chiave nel corso della progressione di diverse tipologie tumorali, incluso il cancro al seno, a cui in particolare anche le proteine HMGA sono state associate. L'obiettivo della Tesi è quindi quello di studiare il ruolo delle proteine HMGA nella transizione epitelio-mesenchimale e in particolare nel cancro al seno. A questo scopo abbiamo sviluppato diversi modelli cellulari di transizione epitelio-mesenchimale. Il primo modello ha previsto la creazione di un sistema stabile di over-espressione della proteina HMGA1 nella linea epiteliale di tumore al seno MCF7. Abbiamo analizzato diversi aspetti della tumorigenesi mediante saggi di migrazione ed invasione in transwell, dimostrando come alti livelli della proteina HMGA1 inducano un aumento di entrambi i processi rispetto ad una condizione di controllo. Inoltre i dati di migrazione sono stati confermati in un sistema inducibile per la over-espressione di HMGA1 nella stessa linea cellulare MCF7 e da saggi condotti in condizione di deplezione di HMGA1 attraverso strategie di silenziamento, dimostrando ulteriormente come la migrazione sia un fenomeno HMGA1 dipendente. Abbiamo inoltre esaminato lo stato di espressione di diversi geni, inclusi specifici marker di transizione epitelio-mesenchimale, mediante analisi di Real Time PCR, osservando un cambiamento verso una condizione di tipo pre-maligno e di parziale transizione ad uno stato mesenchimale. Inoltre è stata verificata la risposta al danno indotto da doxorubicina mediante saggio di colony formation, dimostrando come cellule over-esprimenti HMGA1 possiedano un vantaggio in termini di sopravvivenza e di numero di colonie formate, rispetto alle cellule di controllo. Per approfondire ulteriormente il ruolo esercitato dalle HMGA nella transizione epitelio-mesenchimale, sono stati sviluppati altri due modelli cellulari, uno nella linea epiteliale umana di cancro al seno MDA-MB-468 trattata con EGF (Epidermal Growth Factor), l'altro nella linea cellulare murina mammaria di tipo epiteliale NMuMG, trattata con TGF-β (Transforming Growth Factor-β), in cui l'azione di HMGA2 è stato dimostrato avere un ruolo determinante. Mediante analisi di Real Time PCR di marker di transizione epitelio-mesenchimale, di Western Blot e di immunofluorescenza abbiamo dimostrato l'effettiva solidità di questi modelli cellulari, confermato anche dal fatto che è possibile apprezzare un consistente cambio morfologico verso un fenotipo mesenchimale e una concomitante over-espressione delle proteine HMGA. Da questi modelli è stato quindi possibile evincere come le HMGA siano coinvolte nell'acquisizione di caratteristiche di tipo tumorale anche mediante processi di transizione epitelio-mesenchimale e come questi modelli siano utili al fine di semplificare network molecolari.
XXV Ciclo
1984
ALTAMURA, SANDRO. "IDENTIFICAZIONE E CARATTERIZZAZIONE DI PARTNERS MOLECOLARI DELLE PROTEINE HMGA". Doctoral thesis, Università degli studi di Trieste, 2007. http://thesis2.sba.units.it/store/handle/item/12290.
Pełny tekst źródłaAdair, Jennifer Eileen. "Molecular and genetic influence of HMGA1 proteins on nucleotide excision repair". Online access for everyone, 2005. http://www.dissertations.wsu.edu/Dissertations/Fall2005/j%5Fadair%5F120605.pdf.
Pełny tekst źródłaVogel, Benjamin [Verfasser], i Robert [Akademischer Betreuer] Hock. "Organisation von Chromatin durch HMGA1 Proteine / Benjamin Vogel. Betreuer: Robert Hock". Würzburg : Universitätsbibliothek der Universität Würzburg, 2012. http://d-nb.info/1025223853/34.
Pełny tekst źródłaSGUBIN, MICHELA. "HMGA1-p27-stathmin axis promotes migration in triple-negative breast cancer cells". Doctoral thesis, Università degli Studi di Trieste, 2020. http://hdl.handle.net/11368/2961109.
Pełny tekst źródłaEren, Elif. "HMA2. A Transmembrane Zn2+ Transporting ATPase from Arabidopsis thaliana". Digital WPI, 2007. https://digitalcommons.wpi.edu/etd-dissertations/6.
Pełny tekst źródłaBeuing, Claudia [Verfasser]. "Charakterisierung des Caninen High – Mobility – Group A1 (HMGA1) Gens und Detektion von Punktmutationen / Claudia Beuing". Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2010. http://d-nb.info/1009589687/34.
Pełny tekst źródłaLiau, Siong Seng. "High mobility group A1 (HMGA1) : a novel prognostic indicator and therapeutic target in pancreatic adenocarcinoma". Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/24834.
Pełny tekst źródłaZANIN, ROSSELLA. "HMGA1 AND FOXM1 SYNERGISTICALLY REGULATE A COMMON GENE NETWORK MODULATING THE ANGIOGENESIS IN BREAST CANCER". Doctoral thesis, Università degli Studi di Trieste, 2018. http://hdl.handle.net/11368/2924772.
Pełny tekst źródłaJakimovska, Frosina. "Characterization of the interaction between nucleophosmin (NPM) and highmobility group a (HMGA) proteins". Doctoral thesis, Università degli studi di Trieste, 2008. http://hdl.handle.net/10077/2760.
Pełny tekst źródłaABSTRACT HMGA proteins are members of the high mobility group (HMG) non-histone, architectural chromosomal proteins. The HMGA family consists of: A1a, A1b and A2, the first two being isoforms produced by alternative splicing. These are small proteins, about 100aa residues long, characterized by three basic stretches of AT-hooks which bind to the AT-rich sequences on the DNA minor groove. They are normally present in rapidly proliferating cells (embryo) whereas upon differentiation the levels of these proteins decrease until they are nearly absent from adult cells. Overexpression of these proteins has been correlated with various types of neoplastic transformations. The interaction network of HMGA has been an object of study for years in our laboratory and one of the most intriguing protein-protein interactions studied is the one between HMGA and nucleophosmin. Nucleophosmin (NPM, B23, numatrin or NO38) is one of the most abundant phosphoproteins, mainly localized in the nucleoli but it also shuttles between the nucleus and the cytoplasm. This versatile protein has been proven to be involved in various cellular functions and related to both proliferative and growth-suppressive roles in the cell. The first evidence of the interaction HMGA2-NPM in our lab has been obtained by in vitro assays (affinity chromatography). The step ahead was to see if this interaction occurs in vivo and if it does, to try to find ts functional significance. Thus,immunoprecipitation (IP) experiments were performed.The first one gave the proof thet interaction between HMGA2 protein and NPM (transfected and endogenous) occurs. The second IP gave the evidence that interaction occurs between HMGA1a and NPM too. This in vivo protein-protein interaction was to be given a functional significance. We tested by siRNA HMGA1a treatment if downregulation of HMGA1a expression influences the expression of the SOD2 gene (regulated by NPM). The effect of the HMGA1a silencing has proven to be very slight on the SOD2 gene (a 14% of expression reduction). EMSA experiments have been performed in order to test the effect of NPM on the DNA binding properties of the HMGA2 protein with the DNA probes E3 and HCRII. In both cases it has been observed that NPM increases the DNA binding affinity of the HMGA2 protein.
1979
Zammitti, Salvina. "Post-translational modifications of high mobility group a (HMGA) proteins in neoplastic transformation". Doctoral thesis, Università degli studi di Trieste, 2010. http://hdl.handle.net/10077/3614.
Pełny tekst źródłaLe proteine HMG (High Mobility Group) sono la famiglia più ampiamente e meglio caratterizata fra le proteine cromosomiche non istoniche. Esse sono raggruppate in tre sottofamiglie: HMGA, HMGB ed HMGN. Ciascuna sottofamiglia è caraterizzata da una sequenza o motivo funzionale attraverso il quale sono capaci di legarsi a specifiche strutture sul DNA o sulla cromatina. La famiglia HMGA di mammifero consiste di due geni funzionali: HMGA1 and HMGA2. Lo splicing alternativo del trascritto del gene HMGA1 dà origine alle proteine HMGA1a ed HMGA1b. La proteina HMGA2 è codificata dall’altro gene. Le proteine HMGA partecipano a specifiche interazioni proteina-DNA e proteina-proteina inducendo sia cambiamenti strutturali della cromatina che la formazione di complessi macromolecolari su regioni promotrici//enhancer di diversi geni. Pertanto esse sono descritte come fattori archietturali della trascrizione. Grazie alla loro multifunzionalità, ese partecipano a diversi processi biologici quali l’integrazione virale, l’embriogenesi e la differenziazione, l’apoptosi, la senescenza, la trasformazione neoplastica ed il riparo del DNA. La caratteristica di proteine oncofetali attribuita alle HMGA prende origine dal fatto che esse sono (i) altamente espresse durante l’embriogenesi, (ii) assenti o espresse a bassi livelli nei tessuti adulti e (iii) altamente riespresse nelle cellule trasformate. Queste proteine sono, tra le proteine nucleari, quelle più soggette a modificazioni post-traduzionali e le loro attività sono modulate da una ampia varietà di modificazioni post-traduzionali. In questo lavoro di tesi, grazie all’uso di linee cellulari di cancro mammario in cui è stata indotta la reversione del fenotipo neoplastico tramite trattamento farmacologico e successive analisi di spettrometria di massa, si è ricercata una connessione tra le modificazioni post-traduzionali delle HMGA ed il processo di trasformazione neoplastica. Inoltre, grazie ad una nuova strategia in vitro sviluppata nel nostro laboratorio per l’identificazione di partner molecolari delle proteine HMGA, si è dimostrato che la proteina HMGA1a si associa con la proteina Ku70, che è un fattore chiave coinvolto nel riparo delle rotture al doppio filamento di DNA attraverso il “non-homologous end joining”. Numerose evidenze sperimentali suggeriscono che l’inibizione del riparo del DNA da parte delle HMGA posa contribuire alle instabilità genetiche e cromosomiche comunemente ritrovate nelle celle cancerose. Perciò, si è ricercata una relazione funzionale tra le proteine HMGA e le proteine chiave nel meccanismo di riparo del DNA attraverso “non-homologous end joining”, focalizzando l’attenzione in particolare sulla proteina DNA-PK (DNA-dependent protein kinase), che ha una funzione regolatrice chiave in questo processo.
XXII Ciclo
1973
Bastos, Guilherme de Medeiros. "Detecção de proteínas envolvidas no remodelamento da cromatina de embriões bovinos produzidos in vitro a partir de oócitos oriundos de folículos antrais pequenos e grandes". Universidade Federal de Santa Maria, 2006. http://repositorio.ufsm.br/handle/1/4138.
Pełny tekst źródłaTem sido demonstrado que oócitos de várias espécies adquirem capacidade para completar a maturação meiótica e suportar o desenvolvimento embrionário durante os estágios finais do crescimento folicular. Com o objetivo de investigar diferenças moleculares entre embriões bovinos produzidos a partir de oócitos derivados de folículos pequenos (1-2 mm) e grandes (4-8 mm), dois experimentos foram delineados visando identificar por imunocitoquimica a presença de três fatores reguladores da cromatina envolvidos principalmente nos processos de transcrição e reparo do DNA. No primeiro experimento, foi investigado se o perfil de expressão das proteínas (do inglês) High-Mobility Group N2 (HMGN2) e histona H3 acetilada na lisina 14 (Ac.H3K14) seria alterado pela origem dos oócitos (folículos pequenos vs. folículos grandes) e pelo tempo necessário para realizar a primeira clivagem (<24 h vs. >24 h) após ativação partenogenética (AP). Embriões clivados cedo (até 24 h) e tarde (após 24 h) foram fixados às 36, 50, 60, 70 e 80 h após AP e processados para detectar a HMGN2 ou Ac.H3K14. Os percentuais de maturação nuclear (81% vs. 59%), clivagem cedo (47% vs. 39%) e blastocisto (34% vs. 19%) foram significativamente maiores (P<0,05) nos oócitos oriundos de folículos grandes em comparação aos de folículos pequenos. Os percentuais de núcleos positivos para Ac.H3K14 (61% vs. 38%) e HMGN2 (74% vs. 56%) às 60 h após AP foram maiores (P<0,05) nos embriões produzidos a partir de oócitos de folículos pequenos comparado aos de folículos grandes. Entretanto, um maior percentual de núcleos positivos para HMGN2 (94% vs. 75%; P<0,05) foi detectado em embriões produzidos com oócitos de folículos grandes às 80 h após a AP. Concluiu-se que a proporção de núcleos com sinal positivo para HMGN2 e Ac.H3K14 é dependente do tamanho dos folículos e do tempo transcorrido para os oócitos realizarem a primeira clivagem. No segundo experimento, foi investigado se o perfil de fosforilação da proteína histona H2A.X (γH2A.X), que é um indicador de rompimento da cadeia dupla do DNA, seria diferente em embriões produzidos a partir de oócitos oriundos de folículos pequenos ou grandes. Os oócitos foram submetidos à AP ou fertilização in vitro (FIV) por 18 h e, então, cultivados. A clivagem foi avaliada 24 e 36 h após a AP e 32 e 42 h após FIV. Os embriões clivados foram fixados 36 h após AP e 42 h após FIV, e então processados para detectar a presença da γH2A.X. A maioria dos embriões produzidos a partir de oócitos submetidos à AP e FIV apresentou quantidades detectáveis de γH2A.X, variando entre poucos focos até um sinal completamente difuso no núcleo. A γH2A.X foi detectada em 64% vs. 76% (P<0,05) dos núcleos dos embriões ativados e em 76% vs. 80% (P<0,05) dos núcleos dos embriões de FIV produzidos a partir de oócitos oriundos de folículos pequenos e grandes, respectivamente. Embriões oriundos de FIV que apresentaram número <4 núcleos às 42 h tiveram maiores percentuais (P<0,05) de núcleos positivos para γH2A.X (89% e 85%) do que os que apresentaram número ≥4 núcleos (72% e 62%, respectivamente para folículos pequenos e grandes). Foi demonstrado que a γH2A.X é altamente detectada mas não é diferentemente expressa em embriões bovinos produzidos a partir de oócitos oriundos de folículos pequenos e grandes e submetidos à AP ou FIV. Em geral, os experimentos demonstraram que as proteínas HMGN2, Ac.H3K14 e γH2A.X são expressas durante o desenvolvimento embrionário precoce em bovinos.
Rehbini, Ohoud Mohammedsabri M. "The role of high mobility nucleosomal binding protein (Hmgn2) in undifferentiated mouse epiblast carcinoma stem cells". Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7190/.
Pełny tekst źródłaWinston, Eugenia Michele. "The Utilization of the Hmg2 Inducible Promoter to Genetically Engineer Parasite Resistance in Tobacco". Diss., Virginia Tech, 2003. http://hdl.handle.net/10919/27200.
Pełny tekst źródłaPh. D.
Shama, Bansod. "Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development". Kyoto University, 2017. http://hdl.handle.net/2433/228230.
Pełny tekst źródłaBloch, Mandy [Verfasser]. "HMGA1- als neuer Koregulator der Peroxisomen Proliferator aktivierten Rezeptor gamma- vermittelten Transrepression in humanen Gefäßmuskelzellen / Mandy Bloch". Berlin : Freie Universität Berlin, 2013. http://d-nb.info/1037343069/34.
Pełny tekst źródłaPETROSINO, SARA. "HMGA1 MODULA L'ESPRESSIONE DEGLI ISTONI CICLO CELLULARE-DIPENDENTE, RENDENDO CELLULE RESISTENTI ALL'EPIRUBICINA PIU' SENSIBILI ALLA SUA AZIONE". Doctoral thesis, Università degli Studi di Trieste, 2021. http://hdl.handle.net/11368/2988916.
Pełny tekst źródłaMy research project is focused on the study of a specific subtype of breast cancer (BC), the triple-negative (TNBC), the most aggressive and difficult to treat because of the absence of specific therapeutic options other than chemotherapy. Usually, adjuvant therapy (i.e anthracycline-based regimens) is recommended after surgical intervention of patients affected by TNBC. HMGA1 is involved in the onset and progression of neoplastic transformation, and in chemoresistance. HMGA1 is a key oncogenic factor in TNBC involved in transcriptional and epigenetic regulatory mechanisms. We already demonstrated that HMGA1 can affect histone H1 phosphorylation status in TNBC cells, since HMGA1 depletion leads to dephosphorylation of histone H1. In this thesis, we decided to elucidate the pathway leading to this regulation. Indeed, we performed LC/MS analyses of histone H1 extracted after CCNE2 and CDK2 silencing, the major factors responsible for histone H1 phosphorylation. We demonstrate that HMGA1 modulation of histone H1 phosphorylation goes through a cyclinE2-Cdk2 dependent mechanism. Since histone H1 phosphorylation is cell cycle-dependent and has low phosphorylation in G1-phase and an increased rate in S- and G2-phase with a maximum during mitosis, we hypothesized that HMGA1 could have a role in cell-cycle modulation of histones. We proceeded with histone gene and protein expression analyses in TNBC cells, silenced for HMGA1 expression. Accordingly, we evaluated a decrease in expression of histones at transcriptional and post-transcriptional levels after HMGA1 depletion in TNBC cells. Then, we deeper investigated the hypothesis of a HMGA1 dependent pathway for histone gene expression. We started focusing on specific histone variant (HIST1H4H/H4) modulated after HMGA1 silencing. We demonstrate that HMGA1 directly regulates HIST1H4H histones expression by activating its promoter. Moreover, we disclosed a protein/protein interaction between HMGA1 and NPAT, a master regulator of histone transcriptional expression. After, we analyzed the cell cycle distribution of MDA-MB-231 cells after HMGA1 silencing by flow cytometry. Therefore, we demonstrated that HMGA1 promotes cell-cycle progression in MDA-MB-231 cells and its depletion reduces protein expression of SLBP, a sensor of cell cycle progression. Then, we exploited bioinformatic analyses to search for prognostic and predictive value of HMGA1-regulated histones in BC. Interestingly, we disclosed significantly high expressed histone variants (HIST1H1C/H1.2, HIST1H2AC/H2A1c, HIST1H2BD/H2B1d and HIST1H4H/H4) in BC also enriched in TNBC. Moreover, we observed that HIST1H1C/H1.2 and HIST1H4H/H1.4 had a prognostic value in BC. On the current therapeutic trend and our experimental evidence by which we demonstrate that HMGA1 expression influence cell cycle distribution in MDA-MB-231, we asked whether HMGA1 could be a chemosensitizer factor for a cell-proliferating active drug such as epirubicin. To this end, we generated a TNBC cell line resistant to epirubicin (ER-TNBC) using MDA-MB-231 cells (ER-MDA-MB-231). By the MTS-assay we demonstrated that HMGA1 is a chemosensitizer factor for epirubicin cytotoxic action. After we performed the analysis of the cell cycle distribution of ER-MDA-MB-231 cells by flow cytometry after HMGA1 silencing with respect to control condition. We concluded that HMGA1 favours epirubicin cytotoxic effect through the coordination of the active proliferation. Indeed, we demonstrated that HMGA1 promotes cell-cycle progression in ER-MDA-MB-231 cells. Finally, HMGA1 is involved in epirubicin chemoresistance, at least partially, by affecting the expression of HIST1H4H/H1.4 histone (probably of other as well) and in this way of cell cycle progression. Therefore, we conclude that HMGA1 expression could not be neglected in epirubicin treatment regimens for TNBC-HMGA1 expressing cancer and that could be a valuable mean to predict epirubicin responsiveness in resistance BC cells.
Roemer, Sarah Clark. "Structural and functional analysis of progesterone receptor-DNA interaction /". Connect to full text via ProQuest. IP filtered, 2005.
Znajdź pełny tekst źródłaTypescript. Includes bibliographical references (leaves 165-185). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;