Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer

Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer

Bibliographic Details
Main Author: Ogba, Ndiya
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2010
Subjects:
Biomedical Research
Breast Cancer
HEXIM1
Estrogen Receptor Alpha
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1258406511
id ndltd-OhioLink-oai-etd.ohiolink.edu-case1258406511
record_format oai_dc
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case12584065112021-08-03T05:33:16Z Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer Ogba, Ndiya Biomedical Research Breast Cancer HEXIM1 Estrogen Receptor Alpha <p>Breast cancer is the second leading cause of death in women in the United States, making the search for more therapeutic targets in breast cancer etiology very significant. This aim of this thesis was to further elucidate the function of hexamethylene bisacetamide-inducible protein 1 (HEXIM1) in estrogen (E2)-mediated signaling and mammary gland development and tumorigenesis. In previous work, our laboratory has shown that HEXIM1 inhibits breast cell growth and estrogen receptor-alpha (ERα) transcriptional activity. Other studies have shown that HEXIM1 inhibits the activity of positive transcription elongation factor b (P-TEFb) with functional consequences for gene expression. However, it is not clear whether HEXIM1 regulation of all genes is P-TEFb-dependent and how the P-TEFb-inhibitory function of HEXIM1 ties into mammary gland development or tumorigenesis—which is the main focus of the work described therein. </p><p> We demonstrate that HEXIM1 regulates E2-driven transcriptional activity of ERα and P-TEFb within the context of some ERα target genes. P-TEFb inhibition correlated with a decrease in expression of ERα target genes, cyclin D1 and pS2. Cyclin D1 plays a major role in the cell cycle and tumorigenesis. In the mammary gland, we found that increased HEXIM1 expression decreased ductal branching, an E2/ERα-driven process and decreased cyclin D1 expression. </p><p> Additionally, recent work in our laboratory uncovered a novel role for HEXIM1 during heart and vascular development via the regulation of the vascular endothelial growth factor (VEGF). VEGF is a cytokine that regulates the formation of blood vessels and it represents a major target for tumor therapy. In this thesis, we demonstrate that HEXIM1 regulates VEGF expression in a P-TEFb-independent manner in breast epithelial cells by decreasing E2/ERα-induced expression of hypoxia-inducible factor 1 alpha (HIF-1α), a potent inducer of VEGF. In the mammary gland and during tumorigenesis, HEXIM1 plays a role in regulating HIF-1α and VEGF expression and related-angiogenesis. </p><p> Overall, the studies provide insight into the role of HEXIM1 in regulating E2/ERα gene expression in breast cancer cells and in the mammary gland. Ultimately, we hope that the collective of this work demonstrates therapeutic potential for HEXIM1 given its anti-proliferative and anti-angiogenic functions in vivo.</p> 2010-01-23 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1258406511 http://rave.ohiolink.edu/etdc/view?acc_num=case1258406511 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biomedical Research
Breast Cancer
HEXIM1
Estrogen Receptor Alpha
spellingShingle Biomedical Research
Breast Cancer
HEXIM1
Estrogen Receptor Alpha
Ogba, Ndiya
Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer
author Ogba, Ndiya
author_facet Ogba, Ndiya
author_sort Ogba, Ndiya
title Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer
title_short Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer
title_full Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer
title_fullStr Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer
title_full_unstemmed Transcriptional Regulation Of Estrogen Receptor Alpha Target Genes By Hexamethylene Bisacetamide-Inducible Gene 1 (HEXIM1) And Its Role In Mammary Gland Development And Breast Cancer
title_sort transcriptional regulation of estrogen receptor alpha target genes by hexamethylene bisacetamide-inducible gene 1 (hexim1) and its role in mammary gland development and breast cancer
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2010
url http://rave.ohiolink.edu/etdc/view?acc_num=case1258406511
work_keys_str_mv AT ogbandiya transcriptionalregulationofestrogenreceptoralphatargetgenesbyhexamethylenebisacetamideinduciblegene1hexim1anditsroleinmammaryglanddevelopmentandbreastcancer
_version_ 1719421678998519808

Similar Items