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Estrogen Nuclear Receptor Coactivators In Pathogenesis Of Breast Cancer
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Book Synopsis Estrogen Nuclear Receptor Coactivators in Pathogenesis of Breast Cancer by :
Download or read book Estrogen Nuclear Receptor Coactivators in Pathogenesis of Breast Cancer written by and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This project focuses on the role of nuclear receptor coactivators in steroid dependent regulation of cell growth in pathogenesis of breast cancer. A novel nuclear receptor coactivator of transcription, p300 and CBP associated factor (p/CAF) has been shown to be required for estrogen, thyroid hormone, and retinoic acid-dependent gene expression. The histone acetyltransferase activity of p/CAF was demonstrated to play essential role in nuclear receptor dependent gene expression and it appeared to be transcription factor specific. The ligand-dependent association of p/CAF with nuclear receptor depends upon nuclear receptor corepressor (NCoR) dismissal. These data suggest that p/CAF complex plays a central role in nuclear receptor dependent gene regulation, a key element in steroid dependent cancer development.
Book Synopsis The Role of Estrogen Related Receptor in Modulating Estrogen Receptor Mediated Transcription in Breast Cancer Cells by :
Download or read book The Role of Estrogen Related Receptor in Modulating Estrogen Receptor Mediated Transcription in Breast Cancer Cells written by and published by . This book was released on 2004 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: Unlike most nuclear receptors, the Estrogen Receptor-Related Receptors (ERRs) activate transcription constitutively, interacting with coactivators and target gene promoters in the absence of ligand. Structurally, this subfamily of receptors is related to the classical estrogen receptors and has been shown to positively regulate the transcription of several estrogen responsive genes. Interestingly, the transcriptional activity of ERRalpha is not inhibited by classical anti-estrogens suggesting that its ability to regulate ER- responsive genes may contribute to the development of tamoxifen resistant breast cancer. Without pharmacological agents to regulate ERRalpha activity it has been difficult to define the specific roles of this orphan receptor in the pathogenesis of breast cancer and thus its potential as a therapeutic target is unknown. To address this issue we have developed approaches to both positively and negatively regulate ERRalpha activity in target cells. Specifically, we have developed peptide antagonists to inhibit ERRalpha activity by blocking cofactor binding and have developed activating "protein ligands" by creating modified coactivators that selectively regulate ERRalpha transcriptional activity. With these tools, we have characterized the critical regions of the receptor important for coactivator binding and defined differential binding requirements between coactivator families. In addition, we are identifying the target genes and processes regulated by ERRalpha.
Book Synopsis Estrogens, Estrogen Receptor and Breast Cancer by : Fritz F. Parl
Download or read book Estrogens, Estrogen Receptor and Breast Cancer written by Fritz F. Parl and published by IOS Press. This book was released on 2000 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogens have been implicated to play a role in the development of breast cancer. The purpose of this book is to provide a comprehensive analysis of experimental, clinical and epidemiological evidence in support of the carcinogenicity of estrogens.
Download or read book Seikkailu- ja ajanvietesarja written by and published by . This book was released on 1946 with total page 23 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Concentration-dependent Estrogen Receptor-alpha Transcriptional Function in Breast Cancer by : Amy M. Fowler
Download or read book Concentration-dependent Estrogen Receptor-alpha Transcriptional Function in Breast Cancer written by Amy M. Fowler and published by . This book was released on 2005 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Role of Steroid Receptor Coactivator-1 in Breast Cancer by : Neil J. McKenna
Download or read book The Role of Steroid Receptor Coactivator-1 in Breast Cancer written by Neil J. McKenna and published by . This book was released on 2001 with total page 33 pages. Available in PDF, EPUB and Kindle. Book excerpt: The role of steroid receptor coactivator-1 (SRC-1) in breast cancer is primarily a function of (i) the expression patterns of nuclear receptors (NRs) and SRC family members in the tumor, and (ii) their inherent interaction affinities. An outstanding question is the extent to which SRC/NR pathways in breast cancer are uncoupled by administration of selective estrogen receptor modulator (SERM) regimens such as 4-hydroxytamoxifen. An appreciation of the role of SRC-1 and other SRCs in the selective recruitment of NRs during the development of breast cancer is a prerequisite for the design of novel SRMs for treatment of breast cancer. We used BlAcore analysis to monitor interactions between SRCs and His-tagged NRs. Distinct affinities were noted for different NR-coactivator interactions, indicating an interaction preference spectrum for estrogen receptor-alpha (ERalpha) of SRC-3>SRC-1>SRC-2. The interaction of ERalpha with SRC family members was differentially influenced by different SERMs. In all cases, the interaction between ERalpha and SRCs was promoted by 17beta-estradiol and inhibited by 4-hydroxytamoxifen, raloxifene and ICI 182, 780. The interaction kinetics of SRC family members with liganded NRs are consistent with a bipartite model involving a transitional intermediate. By providing accurate measurements of the modulation by SRMs of the interaction between NRs and SRC family members, we have created a model system within which rational design of SERMs for breast cancer treatment can be evaluated in a functional context.
Book Synopsis Estrogen Receptor and Breast Cancer by : Xiaoting Zhang
Download or read book Estrogen Receptor and Breast Cancer written by Xiaoting Zhang and published by Springer. This book was released on 2018-10-16 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery of ER by Dr. Elwood Jensen exactly 60 years ago has not only led to the birth of a whole new vital nuclear receptor research field but also made a rapid, direct and lasting impact on the treatment and prevention of breast cancer. Since that landmark discovery, tremendous progress has been made in our understanding of the molecular functions of ER and development of targeted therapies against ER pathways for breast cancer treatment. However, there is currently no book available addressing these discoveries and recent advancement in a historical and systematic fashion. This book is intended to provide comprehensive, most up-to-date information on the history and recent advancement of ER and breast cancer by world renowned leaders in the field. These chapters include the history of the discovery of ER; physiological and pathological roles of ER; recent discovery of ER cistrome, transcriptome and its regulation of noncoding RNAs such as microRNAs and enhancer RNAs in breast cancer; development and clinical practices of the first targeted therapy Tamoxifen and other antiestrogens for breast cancer treatment; structural basis of ER and antiestrogen actions; molecular insights into endocrine resistance; the role of ER mutants, ER-beta and environmental estrogens in breast cancer; and emerging state-of-the-art therapeutic approaches currently in development to overcome treatment resistance and future perspectives. The book will provide undergraduate and graduate students, basic scientists and clinical cancer researchers, residents, fellows, as well as clinicians, oncology educators and the general public a thorough and authoritative review of these exciting topics.
Book Synopsis Estrogen-Related Receptor Alpha (ERRa)-Coactivator Interactions as Targets for Discovery of New Anti-Breast Cancer Therapeutics by :
Download or read book Estrogen-Related Receptor Alpha (ERRa)-Coactivator Interactions as Targets for Discovery of New Anti-Breast Cancer Therapeutics written by and published by . This book was released on 2006 with total page 12 pages. Available in PDF, EPUB and Kindle. Book excerpt: The nuclear receptor estrogen receptor alpha (ERalpha) is a primary focus of the therapy of breast cancers. ERalpha-positive breast cancers have traditionally been treated with the anti-estrogen tamoxifen, or with inhibitors of aromatase. ERalpha-negative breast cancers do not respond to anti-estrogen treatment; instead, current therapeutics, such as Herceptin, have focused on the transmembrane tyrosine kinase receptor ErbB2 (HER2) because it is often overexpressed in ERalpha-negative tumors and correlates with a poor prognosis. Estrogen-related receptor alpha (ERRalpha) has sequence similarity to ERalpha, but ERRalpha does not bind estrogens. In some cases ERRalpha is constitutively active, which is likely determined not only by its interaction with coactivators, but also in part by post-translational modifications occurring via the ErbB2 (HER2) signaling pathways. Thus, ERRalpha probably plays a key role in the etiology and progression of a subset of breast cancers. We believe that the ERRalpha-coactivator interaction is a promising target for new chemotherapeutic drug development. We have generated and characterized a set of murine monoclonal antibodies for use in studying the biology of ERRalpha. We are now using some of those antibodies in gentle immunoaffinity chromatography to determine ERRalpha-associated proteins. Using in vitro assays, we will study the binding properties of ERRalpha with known coactivators like transcriptional intermediary factor 2 (TIF2), as well as any ERRalpha-associated proteins we may find during immunopurification. In the future, using a luminescence resonance energy transfer-based high-throughput screen previously developed in our laboratory, we hope to identify small molecules that interfere with the binding of ERRalpha with these coactivators.
Book Synopsis An Estrogen Receptor-Selective Coactivator: A Potential Regulator of Tamoxifen Effectiveness in Breast Cancer Treatment and Prevention by :
Download or read book An Estrogen Receptor-Selective Coactivator: A Potential Regulator of Tamoxifen Effectiveness in Breast Cancer Treatment and Prevention written by and published by . This book was released on 2002 with total page 17 pages. Available in PDF, EPUB and Kindle. Book excerpt: The estrogen receptor (ER) is involved in breast cancer development and progression. We have isolated a novel 97 kDa DEAD box RNA helicase (DP97) that interacts with the estrogen receptor alpha (ERa) in the presence of either estradiol or trans-hydroxytamoxifen. DP97 represses the transcriptonal activity of the estradiol-occupied estrogen receptor and this repression can be relieved with Trichostatin A(TSA), a selective histone deacetylase inhibitor. DP97 represses the activity of a constitutive SV4O promoter when it is recruited as a Gal-4 DNA binding domain fusion protein. DP97 also interacts with, and represses the activity of, other nucelar receptors such as the progesterone receptor b, glucocorticoid receptor, and retionic acid receptor a. However, DP97 does not repress the activity of either p53 or VP16. We show that the N- terminal helicase region of DP97 is dispensible for its activity as a transcriptional repressor. Furthermore, a BLAST homology search of the remaining sequence of p97 reveales that this protein has a small region of homology with the SMRTe(NCoR2) corepressor protein. This small region is also able to repress a constitutively active SV4O promoter when it is recmited to it as a Gal-4 DNA binding domain fusion protein. Therefore, DP97 functions as a RNA helicase, a nuclear receptor interacting protein, and as a transcriptional coregulator.
Book Synopsis Nuclear Receptors and Genetic Disease by : Thomas P. Burris
Download or read book Nuclear Receptors and Genetic Disease written by Thomas P. Burris and published by Academic Press. This book was released on 2000-09-06 with total page 437 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nuclear Receptors and Genetic Disease provides the first compilation of the role of nuclear hormones in health and disease and incorporates the latest breakthroughs in the field. It provides comprehensive reviews of the major receptors prepared by the acknowledged experts in each area. Each chapter provides information on the history, physiology, structure, mechanism of action, genetics, pathophysiology, disease diagnosis, and disease treatment for a particular nuclear receptor. Each chapter also includes a table showing all the known mutations of the respective nuclear receptor with the corresponding clinical disorder.Receptors included in this book are: - The Nuclear Receptor Superfamily - Thyroid Hormone Receptors - Estrogen and Progesterone Receptors - The Androgen Receptor - DAX-1 and Related Orphan Receptors - The Vitamin D Receptor - Retinoid Receptors - Mineralocorticoid and Glucocorticoid Receptors - Hepatocyte Nuclear Factor 4 a - Peroxisome Proliferator Activated Receptors - Coactivators and Corepressors
Book Synopsis Hormone Receptors in Breast Cancer by : Suzanne A. W. Fuqua
Download or read book Hormone Receptors in Breast Cancer written by Suzanne A. W. Fuqua and published by Springer Science & Business Media. This book was released on 2008-12-10 with total page 289 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hormone Receptors in Breast Cancer provides an up-to-date resource of the role of hormone receptors in breast cancer written in depth for both the basic molecular academic researcher and translational scientist. Advances in basic science of molecular endocrinology have undoubtedly been translated into clinical practice, and clinicians caring for this disease need to be knowledgeable about these developments. The molecular basis of hormone action has been elucidated, and the relative significance of the different estrogen and progesterone receptor isoforms has been explored. This explosion of information has lead to exciting new areas of gene specific targeting of the disease, and breast cancer prevention. Paradigm shifts in treatment options and sequencing have recently occurred in breast cancer management, necessitating close cooperation and communication between translational scientists and physicians. This book is focused on providing this communication.
Book Synopsis Inhibition of Estrogen Receptor Coactivator Expression by Antisense Oligodeoxynucleotides and Effect on Breast Cancer Cell Proliferation and Gene Expression by :
Download or read book Inhibition of Estrogen Receptor Coactivator Expression by Antisense Oligodeoxynucleotides and Effect on Breast Cancer Cell Proliferation and Gene Expression written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Coactivators are nuclear proteins that interact with steroid receptors, such as estrogen receptor-alpha (ERalpha), and are required for the ability of receptors to stimulate the expression of target genes. Antiestrogen ligand are commonly utilized in the treatment of breast cancer to negatively regulate the activity of steroid receptors. However, tumors often can develop resistance to antiestrogen therapy. Therefore, as an alternative approach to inhibiting ERalpha function in breast cancer cells, we have developed antisense oligonucleotides against three of the major ERalpha coactivator proteins. These oligonucleotides decrease the expression of coactivator mRNA and protein, and in so doing, decrease the ability of ERalpha to stimulate gene expression. These oligonucleotides also decrease the proliferation of MCF-7 breast cancer cells in response to estrogen treatment. Taken together, anti sense oligonucleotide technology has the potential to regulate ERalpha action at a level that circumvents ligand control, and therefore represents a novel mechanism by which to inhibit breast cancer gene expression and proliferation, and potentially to regulate the growth of breast cancer.
Book Synopsis Nuclear Receptors Coregulators And Human Diseases by : Rakesh Kumar
Download or read book Nuclear Receptors Coregulators And Human Diseases written by Rakesh Kumar and published by World Scientific. This book was released on 2008-03-14 with total page 615 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book serves as a treasure for all those who have an interest in nuclear receptor coregulators and human diseases. Written by experts in the field, each chapter provides comprehensive, up-to-date information on the physiologic and pathologic roles of coregulators in specific organ systems, giving biomedical students; basic and clinical researchers; and educators in diverse sub-specialties a thorough summary of the overall subject. Readers will be able to understand the important current information and views on specific coactivators and corepressors and their roles in the pathogenesis of human diseases in areas outside their own expertise or experience. A special emphasis is placed on the “classic” papers as well as perspectives on future directions for the field.
Book Synopsis Selective Estrogen Receptor Modulators by : Andrea Manni
Download or read book Selective Estrogen Receptor Modulators written by Andrea Manni and published by Springer Science & Business Media. This book was released on 2002-01-18 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: Experimental and clinical researchers from a wide range of disciplines present a wealth of fresh scientific information on the biochemistry, molecular biology, pharmacology, and clinical activity of SERMs. The basic science chapters of the book focus-with an eye to the development of the ideal SERM-on the complex mechanisms of estrogen action, including ligand-dependent conformational changes in alpha and beta, and the recruitment of co-activators and co-repressors which modulate the estrogen receptor transcriptional activity and contribute to its crosstalk with growth factor signaling. The clinical presentation reviews the data accumulated on currently available SERMs, primarily tamoxifen and raloxifene, in cancer treatment and prevention, as well as their effects on the reproductive, vascular, skeletal, and central nervous systems. A tentative approach to menopause-related health issues is also provided for women with and without a previous diagnosis of localized breast cancer.
Book Synopsis Identification of an Estrogen Receptor Variant in Estrogen Independent And/or Tamoxifen Resistant Human Breast Cancer Cell Lines by : Feng Han
Download or read book Identification of an Estrogen Receptor Variant in Estrogen Independent And/or Tamoxifen Resistant Human Breast Cancer Cell Lines written by Feng Han and published by . This book was released on 2001 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Estrogen Action, Selective Estrogen Receptor Modulators And Women's Health: Progress And Promise by : V Craig Jordan
Download or read book Estrogen Action, Selective Estrogen Receptor Modulators And Women's Health: Progress And Promise written by V Craig Jordan and published by World Scientific. This book was released on 2013-05-27 with total page 544 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents the evolution of the authors' ideas about estrogen action and its modulation by a new group of drugs called SERMs (Selective Estrogen Receptor Modulators). The pioneering SERMs — tamoxifen and raloxifene — are known to have saved the lives of millions of women around the world and improved the health of millions more. Estrogen is the central hormone of women's health and reproduction. The book is a journey through 40 years of discovery and success in advancing women's health, with the prospect of improved innovation through medicinal chemistry for the future.
Book Synopsis NR Coregulators and Human Diseases by : Rakesh Kumar (Ph. D.)
Download or read book NR Coregulators and Human Diseases written by Rakesh Kumar (Ph. D.) and published by World Scientific. This book was released on 2008 with total page 615 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book serves as a treasure for all those who have an interest in nuclear receptor coregulators and human diseases. Written by experts in the field, each chapter provides comprehensive, up-to-date information on the physiologic and pathologic roles of coregulators in specific organ systems, giving biomedical students; basic and clinical researchers; and educators in diverse sub-specialties a thorough summary of the overall subject. Readers will be able to understand the important current information and views on specific coactivators and corepressors and their roles in the pathogenesis of human diseases in areas outside their own expertise or experience. A special emphasis is placed on the OC classicOCO papers as well as perspectives on future directions for the field. Sample Chapter(s). Chapter 1: Nuclear Receptor Coregulators in Human Diseases (839 KB). Contents: Nuclear Receptor Coregulators in Human Diseases (R B Lanz et al.); p160 Coactivators: Critical Mediators of Transcriptional Activation by Nuclear Receptors (J H Kim & M R Stallcup); Regulation of Nuclear Hormone Receptor Functions by Ubiquitin-Proteasome Pathway (A Ismail et al.); Coregulators as Oncogenes and Tumor Suppressors (R Kumar & A E Gururaj); A Central Role of SRC-3/AIB1 in Tumorigenesis (J Yan et al.); Thyroid Hormone Receptors, Coregulators, and Disease (M L Privalsky); Androgen Receptor Coactivators in Prostate Cancer (N L Weigel & I U Agoulnik); PGC-1 and Metabolic Control in Skeletal and Cardiac Muscle (Z Arany & B M Spiegelman); Coregulators in Metabolic and Neurodegenerative Diseases (J N Feige et al.); Role of the RIP140 Corepressor in Metabolic Regulation (M G Parker et al.); Nuclear Receptor Corepressors and Metabolism (T Alenghat & M A Lazar); Coregulators in CNS Function and Disease (O C Meijer & E R de Kloet); Tissue Repair and Cancer Control Through PPARs and Their Coregulators (L Michalik & W Wahli); Coregulators and Inflammation (S Ghisletti & W Huang); Nuclear Receptor Coactivators in the Cardiovascular System (J-M Xu); Coregulators as Determinants of Selective Receptor Modulator (SRM) Activity (M C Pace & C L Smith); Coregulators in Toxicology (J Regg et al.); Nuclear Receptor Coactivators Co-ordinate Metabolic Responses to Hormonal and Environmental Stimuli (R M Evans et al.); Nuclear Receptor Cofactor Interactions as Targets for New Drug Discovery (L L Grasfeder & D P McDonnell). Readership: Academic, medical students, residents, fellow and biomedical research students."
