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Epigenetic Regulation By Estrogen Receptor In Breast Cancer Cells
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Book Synopsis Epigenetic Regulation by Estrogen Receptor in Breast Cancer Cells by : Athéna Sklias
Download or read book Epigenetic Regulation by Estrogen Receptor in Breast Cancer Cells written by Athéna Sklias and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Previous epidemiological and experimental studies have strongly implicated estrogens in breast cancer risk and Estrogen Receptor (ER), the transcription factor to which estrogen binds, is considered as the major molecular driver of around 70% breast cancers. The importance of the deregulated estrogen signalling is further highlighted by increasing evidence that current chemopreventive and therapeutic strategies that target hormonally responsive breast cancers frequently result in the development of resistance to anti-estrogens and metastatic progression, highlighting the need for understanding the molecular underlying mechanisms. While until recently, ER was believed to act as a stand-alone transcription factor, which can directly bind its motifs in DNA, it is now accepted that ER activity is a complex and dynamic process that requires highly concerted actions of a dozen transcriptional cofactors and various chromatin regulators at DNA. Recent studies focused on characterising ER-associated cofactors and their role in opening the chromatin provided a remarkable insight into transcriptional regulation mediated by ER. However DNA methylation and histone acetylation are poorly understood in the context of ER's dynamic binding. In this thesis, I combined a cell culture protocol adapted for studying estradiol (E2) deprivation and re-stimulation in stricto sensu in ER-positive breast cancer cells with the latest methylation array, that allowed a genome-wide interrogation of DNA methylation (including a comprehensive panel of enhancers). I further investigated histone acetylation (ChIP-seq) and transcriptome (RNA-seq) after E2 deprivation and re-stimulation to better characterise the ability of ER to coordinate gene regulation. I found that E2 deprivation and re-stimulation result in time-dependent DNA methylation changes and in histone acetylation across diverse genomic regions, many of which overlap with enhancers. Further enrichment analysis of transcription factor (TF) binding and motif occurrence highlights the importance of ER tethering mainly through two partner TF families, AP-1 and FOX, in the proximity of enhancers that are differentially methylated and acetylated. This is the first study that comprehensively characterized DNA methylation at enhancers in response to inhibition and activation of ER signalling. The transcriptome and genome occupancy data further reinforced the notion that ER activity may orchestrate a broad transcriptional programme through regulating a limited panel of critical enhancers. Finally, the E2 re-stimulation experiments revealed that although the majority of the observed epigenetic changes induced by E2 deprivation could be largely reversed when the cells were re-stimulated we show that DNA hypermethylation and H3K27 acetylation at enhancers as well as several gene expression changes are selectively retained. The partial reversibility can be interpreted as a sign of treatment efficiency but also as a mechanism by which ER activity may contribute to endocrine resistance. This study provides entirely new information that constitutes a major advance in our understanding of the events by which ER and its cofactors mediate changes in DNA methylation and chromatin states at enhancers. These findings should open new avenues for studying role of the deregulated estrogen signalling in the mechanism underlying the “roots” of endocrine resistance that commonly develops in response to anti-estrogen therapy.
Book Synopsis Epigenetic Basis for the Regulation of Estrogen Receptor Alpha Activity in Breast Cancer Cells by :
Download or read book Epigenetic Basis for the Regulation of Estrogen Receptor Alpha Activity in Breast Cancer Cells written by and published by . This book was released on 2009 with total page 47 pages. Available in PDF, EPUB and Kindle. Book excerpt: A key factor involved in breast cancer development and progression is the estrogen receptor alpha (ER). Genome-wide computational studies on ER have identified over 70,000 putative Estrogen Response Elements (EREs) in the human genome. However, a genome-wide functional study using ChIP-Chip, has indicated that less than 1/10 of all putative ER binding sites are recognized by the receptor following estrogen stimulation in breast cancer cells. Through genome-wide positional analyses, we demonstrate that ER recruitment is dependent on a specific epigenetic signature characterized by mono and dimethylation of lysine 4 on histone 3 (H3K4me1/me2). Furthermore the pioneer factor FoxA1 translates this epigenetic signature into changes in chromatin structure in a cell type-specific manner for transcription factors, such as ER. Hence, this allows for the establishment of lineage-specific transcriptional enhancers and programs.
Book Synopsis Epigenetic Regulation of Cancer - Part A by :
Download or read book Epigenetic Regulation of Cancer - Part A written by and published by Elsevier. This book was released on 2023-09-02 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Epigenetic Regulation of Cancer, a series of volumes from the International Review of Cell and Molecular Biology series, various experts in epigenetics critically cover multiple facets of cancer-associated epigenetic alterations, including the impact of epigenetic deregulation in all steps of oncogenesis as well as promising strategies to therapeutically target cancer-associated epigenetic deregulation. This collection aims at expanding our knowledge on this exciting field of investigation and providing fresh insights as a basis for further investigations that will hopefully translate into an improved clinical management of patients with cancer. - The collection provides accurate and critical review articles from invited experts on the selected topic - Each review provides the newest insights and remarks on multiple subjects of the topic - The volume offers a broad range of perspectives on detailed features
Book Synopsis Gene Regulation, Epigenetics and Hormone Signaling by : Subhrangsu S. Mandal
Download or read book Gene Regulation, Epigenetics and Hormone Signaling written by Subhrangsu S. Mandal and published by John Wiley & Sons. This book was released on 2017-05-09 with total page 688 pages. Available in PDF, EPUB and Kindle. Book excerpt: Das erste Referenzwerk dieser Art mit einer umfassenden und dennoch prägnanten Einführung in die Epigenetik beschäftigt sich mit den unzähligen Interaktionen zwischen Hormonregulation und Epigenetik. Die Inhalte sind gut strukturiert. Es gibt keine Überschneidungen zwischen den Kapiteln und jedes Kapitel beinhaltet Zusatzmaterialien für Präsentationen. Der Schwerpunkt liegt durchgängig auf Erkrankungen. Zielgruppe sind die vielen Physiologen und Entwicklungsbiologen, die zwar mit der Bedeutung und den Mechanismen der Hormonregulation vertraut sind, aber über unzureichendes Hintergrundwissen im Bereich Epigenetik verfügen.
Book Synopsis Alcohol Promotes Mammary Tumor Development Through Regulation of Estrogen Signaling by : Amy W. Wong
Download or read book Alcohol Promotes Mammary Tumor Development Through Regulation of Estrogen Signaling written by Amy W. Wong and published by . This book was released on 2012 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is the most common malignancy affecting women and the second leading cause of death among women in the United States. Alcohol consumption is one of the few modifiable risk factors for breast cancer development but the mechanism by which it contributes to mammary cancer development and progression remains unclear, although it has been suggested that estrogen is critical for this process. To determine if alcohol promotes mammary tumor development via the estrogen pathway, estrogen receptor alpha-negative (ER[alpha]-negative) MMTV-neu mice were treated with various doses of ethanol and activation of estrogen signaling was measured. Our results showed that alcohol consumption increased estrogen signaling activation, serum estrogen levels and, most interestingly, expression of ER[alpha] in tumor tissue in the ER[alpha]-negative mice. Several lines of evidence in literature suggest that ER[alpha] expression in ER[alpha]-negative cancer cells is inhibited through epigenetic regulation. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than DNA sequence changes. Thus, to determine whether alcohol may regulate ER[alpha] re-expression in ER[alpha]-negative breast cancer cells through epigenetic mechanisms, we examined the effects of ethanol on CpG methylation and histone modifications (acetylation and methylation) of two ER[alpha]-negative breast cancer cell lines, MDA-MB-231 (human) and MMTV-neu (mouse). We also examined whether the epigenetic modifications subsequently affect the recruitment of transcriptional regulation complexes to the ER[alpha] promoter to regulate ER[alpha] transcription. Results showed that alcohol promotes ER[alpha] re-expression in these ER[alpha]-negative cell lines and that this effect was associated with decreased CpG methylation, an overall increase of histone acetylation and decrease of histone methylation, and an alteration in the enrichment of the ER[alpha] transcriptional regulation complexes (pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1) at the ER[alpha] promoter, which may contribute to cancer cell progression. In addition, we found that the inhibition of ER[alpha] by tamoxifen specifically blocks the effects of alcohol on ER[alpha] reactivation. To determine how alcohol promotes cell invasive ability, a critical process for cancer progression, we examined the role of two genes, metastasis suppressor Nm23 and integrin alpha-5 ITGA5, which we identified to be important for alcohol-induced breast cancer cell invasion. It has previously been shown that estrogen may regulate Nm23 expression and that estrogen regulation may be important for ITGA5-mediated cancer progression. Our results showed that alcohol promotes cancer cell invasion through the down-regulation of Nm23, which led to the subsequent increase of ITGA5 and increase of cell invasion. Collectively, data from my research strongly supports and provides evidence that alcohol promotes breast cancer development and progression through the regulation of estrogen signaling.
Book Synopsis Molecular basis of epigenetic regulation in cancer therapies by : Ángeles Carlos Reyes
Download or read book Molecular basis of epigenetic regulation in cancer therapies written by Ángeles Carlos Reyes and published by Frontiers Media SA. This book was released on 2023-02-10 with total page 313 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Epigenetic Regulation of Cancer-Part C by :
Download or read book Epigenetic Regulation of Cancer-Part C written by and published by Elsevier. This book was released on 2024-08-23 with total page 234 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Regulation of Cancer, Part C, Volume 389 in the International Review of Cell and Molecular Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of hot topics, including Epigenetic biomarkers in breast cancer, Contribution of epigenetics to virus-driven cancer, Cancer metabolism and epigenetics, Technologies for epigenome editing, Epigenetics and cancer stemness, Epigenetic modifications in obesity-associated cancers, Epigenetics in cf microRNA in blood of solid tumors, Integrative analysis of transcriptome, chromatin accessibility, cell surface antigen in single cell level for AML, and more.Additional chapters cover Epigenetics in lung cancer, Gene Regulatory Mechanisms underlying therapy resistance in Cancer, Role of miRNAs as epigenetic regulators of immune checkpoints in cancer immunity, Epigenetic contributions to Acute myeloid leukemia (AML), Contribution of epigenetics to chemoresistance, Epigenetic contribution to the relationship between obesity and cancer, and Epigenetic regulation in ovarian cancer. - Provides the latest information on cancer research - Offers outstanding and original reviews on a range of cancer research topics - Serves as an indispensable reference for researchers and students alike
Book Synopsis The Role of Histone Variant H2A.Z in the Regulation of Gene Expression in Breast Cancer Cells by : Luca Bellucci
Download or read book The Role of Histone Variant H2A.Z in the Regulation of Gene Expression in Breast Cancer Cells written by Luca Bellucci and published by . This book was released on 2013 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: During my PhD, I studied the mechanisms of regulation of gene expression in breast cancer. In particular, I was interested in the epigenetic regulation of p21 gene expression in an estrogen receptor negative breast cancer cells (MDA-MB231 cells). We found that in these cells a TSA treatment stimulated p21 expression and increased acetylation of H2A.Z present at the p21 promoter. H2A.Z was strongly associated with the transcription start site of p21. Moreover, depleting the cellular pool of H2A.Z compromised p21 activation and response to HDACi. Acetylation of H2A.Z rather than its association of regulatory element per se was important for p21 expression. My studies led to a publication (Bellucci et al., 2013 [1]) which shows that p21 gene activation in MDA-MB231 cells is p53-independent and controlled by the H2A.Z histone variant and its acetylation. Normally, activation of p21 expression can be p53-independent or dependent, according to the cell system used. But the mechanism behind p21 activation, via HDACi, remains poorly understood. Moreover, p21 regulation depends on the binding of the histone variant H2A.Z. Using the Cyclin D1 gene as a model, I also participated in a project, which shows how, in this case too, H2A.Z acetylation is critical for gene regulation in estrogen receptor positive and negative breast cancer cells. We identified the enzymes involved in H2A.Z acetylation (Tip60) and in chromatin remodeling (Tip48), to propose a model for transcription activation of this gene.
Book Synopsis Transcriptional and Epigenetic Regulation of Oestrogen Signalling in Breast Cancer Cells by : Jing Bi
Download or read book Transcriptional and Epigenetic Regulation of Oestrogen Signalling in Breast Cancer Cells written by Jing Bi and published by . This book was released on 2013 with total page 198 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Epigenetic Regulation of Cancer - Part A by :
Download or read book Epigenetic Regulation of Cancer - Part A written by and published by Elsevier. This book was released on 2023-09 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Regulation of Cancer - Part A, Volume 380 in the International Review of Cell and Molecular Biology series, presents content from various experts in epigenetics who cover multiple facets of cancer-associated epigenetic alterations, including the impact of epigenetic deregulation in all steps of oncogenesis as well as promising strategies to therapeutically target cancer-associated epigenetic deregulation. Specific chapters cover Epigenetic regulation of epithelial-mesenchymal transition during cancer development, Novel insights into DNA methylation-based epigenetic regulation of breast tumor angiogenesis, Super-enhancer landscape rewiring in cancer: The epigenetic control at distal sites, Non-coding RNAs in the epigenetic landscape of Cutaneous T-cell lymphoma, and much more.
Book Synopsis Epigenetic Regulation of Nuclear Hormone Receptor DAX-1 by : Michael B. Heskett
Download or read book Epigenetic Regulation of Nuclear Hormone Receptor DAX-1 written by Michael B. Heskett and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of the body such as testes, ovaries, adrenal cortex and breast. In some cases, changes in DAX-1 expression may serve as an indicator of aberrant growth. For example, DAX-1 expression is greatly reduced in ER+ breast cancer patient samples and several ER+ cell lines; however the mechanism leading to this change in DAX-1 expression is unknown. Here, we propose that expression of DAX-1 may be governed by epigenetic mechanisms. We sought to determine whether promoter region CpG island methylation and expression of DAX-1 were inversely related , and if the loss of DAX-1 expression in the breast cancer cell line MCF-7 is due to epigenetic mechanisms. Using gene expression assays and bisulfite sequencing, we have confirmed the relationship between methylation status and DAX-1 expression in MCF7 and A549 cancer cell lines. We have further analyzed the DAX-1 CpG island to observe the presence of epigenetic readers MeCP2 and MBD1 that link methylation to gene repression, suggesting DAX-1 is expressed and regulated differentially by epigenetic mechanisms in the cancer cell lines MCF7 and A549.
Book Synopsis Epigenetic Regulation of Cancer in Response to Chemotherapy by :
Download or read book Epigenetic Regulation of Cancer in Response to Chemotherapy written by and published by Elsevier. This book was released on 2023-03-27 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Regulation of Cancer in Response to Chemotherapy, Volume 158 of the Advances in Cancer Research series, highlights new advances in the field, with this new volume presenting chapters on timely topics, including Epigenetically Programmed Resistance to Chemotherapy and Promotion of Immune Evasion in Cancer, A Role for the Epigenome in Cancer Cell Drug Tolerance, Histone Methylation and X Chromosomal Genes in Metastasis of Breast Cancer, Targeting Epigenetic Regulation Using Small Molecule Inhibitors, Histone Deacetylase Inhibitors as Sanguine Epigenetic Therapeutics against Pugnacious Lung Cancer, From ecology to oncology: To understand cancer stem cell dormancy, ask a Brine shrimp (Artemia), and more. Additional chapters cover Predictive Models of Chemoresistance Generated by Crunching the Public Drug Screen, Epigenomic and Genomic Profiling Datasets via Regression-, Machine Learning, and Knowledge-Based Methods, Probing on the Mechanisms of lncRNAs on Cancer Drug Resistance, Drug Tolerant Persister Cells in Cancer: Current Knowledge and Therapeutic Perspectives, and much more. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Advances in Cancer Research series - Includes the latest information on the Epigenetic Regulation of Cancer in Response to Chemotherapy
Book Synopsis Xenobiotic Regulation of Estrogen and Progesterone Receptor - Mediated Gene Expression by : Lawanda Schief
Download or read book Xenobiotic Regulation of Estrogen and Progesterone Receptor - Mediated Gene Expression written by Lawanda Schief and published by Page Publishing Inc. This book was released on 2020-11-08 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: Have you ever wondered how chemicals in the environment affect cancer? Well, this book can give you some scientific insight on how common pesticide chemicals and industrial waste can affect the growth of breast cancer cells.
Book Synopsis Epigenetic Regulation of Inflammatory Pathways in Cancer and Aging by : Deepavali Chakravarti
Download or read book Epigenetic Regulation of Inflammatory Pathways in Cancer and Aging written by Deepavali Chakravarti and published by Frontiers Media SA. This book was released on 2023-04-03 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Epigenetic Regulation of Cancer - Part B by :
Download or read book Epigenetic Regulation of Cancer - Part B written by and published by Elsevier. This book was released on 2024-04 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Regulation of Cancer, Part B, Volume 383 in the International Review of Cell and Molecular Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of hot topics, including Epigenetic control of cell signaling in cancer stem cells, Genetic and epigenetic features of neuroendocrine prostate cancer and their emerging applications, Epigenetic regulation in pancreatic cancer, Epigenome Editing in Cancer: Advances and Challenges for Potential Therapeutic Options, Inhibition of epigenetic mechanisms in cancer, and Epigenetics as a determinant of radiation response in cancer.
Book Synopsis Elucidation of Chromatin Remodeling Machinery Involved in Regulation of Estrogen Receptor Alpha Expression in Human Breast Cancer Cells by :
Download or read book Elucidation of Chromatin Remodeling Machinery Involved in Regulation of Estrogen Receptor Alpha Expression in Human Breast Cancer Cells written by and published by . This book was released on 2005 with total page 30 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogen receptor alpha (ER) is an epigenetically regulated gene. Inhibitors of DNA methyltransferases (DNMT) and histone deacetylases (HDAC) synergistically activate the methylated ER gene promoter in ER negative MDA-MB-23 1 human breast cancer cells. Using chromatin immunoprecipitation (ChIP), we examined the chromatin status and repressor complex associated with silenced ER and changes in the key regulatory factors during reactivation by inhibitors of DNMT (5-aza-2'deoxycytidine or 5-aza-dC) and HDAC (trichostatin A or TSA). The silencing of ER due to CpG hyperrnethylation correlates with binding of specific methyl-binding proteins, DNA methyltransferases and HDAC proteins. Inhibition of HDAC activity by TSA results in the increased accumulation of hyperacetylated core histones. The activation of ER gene expression by 5aza-dC also involves the release of the repressor complex involving various methyl binding proteins, DNMTs, and HDACl. HDAC and DNMT inhibitors also modulated histone methylation at H3-K9 and H3-K4 to fonn a more open chromatin structure. Together our results impart a befter understanding of molecular mechanisms of chromatin remodeling during ER reactivation by DNMT and HDAC inhibitors.
Book Synopsis Epigenetic Regulation and Tumor Immunotherapy by : Mingzhu Yin
Download or read book Epigenetic Regulation and Tumor Immunotherapy written by Mingzhu Yin and published by Frontiers Media SA. This book was released on 2022-05-27 with total page 263 pages. Available in PDF, EPUB and Kindle. Book excerpt:
