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Estrogen Receptor Accessory Factors In Breast Cancer Cells
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Book Synopsis Estrogen Receptor Accessory Factors in Breast Cancer Cells by :
Download or read book Estrogen Receptor Accessory Factors in Breast Cancer Cells written by and published by . This book was released on 1997 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of this investigation is to test the hypothesis that estrogen agonists and antagonists promote differential transcriptional activity of the estrogen receptor (ER) by altering accessory protein interactions. We have shown that one or more ER-associated proteins (hsp70, PDI, p48, p45) may be required for maximal interaction of ER with specific DNA sites (EREs) in responsive genes and that the same proteins contribute to the magnitude of DNA distortion without altering the direction of the ER-induced bend of ERE-containing DNA fragments, which is toward the major groove of the DNA helix. We have also used the ligand binding domain of the ER (aa 282-595), expressed in bacteria as a GST-fusion protein (GST-LBD), to capture proteins from mammalian cell extracts that associate with the ER. One protein retained by this technique is a kinase that phosphorylates ER only in the presence of estrogen agonists. Phosphoamino acid analysis and manual sequencing of tryptic peptides have identified the site of phosphorylation as serine 559, a putative casein kinase II phosphorylation site.
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.
Book Synopsis Regulatory Mechanisms in Breast Cancer by : Marc E. Lippman
Download or read book Regulatory Mechanisms in Breast Cancer written by Marc E. Lippman and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 455 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Breast Cancer: Cellular and Molecular Biology [Kluwer Academic Pub lishers, 1988], we tried to present an introduction to the emerging basic studies on steroid receptors, oncogenes, and growth factors in the regulation of normal and malignant mammary epithelium. The response to this volume was superb, indicating a tremendous interest in basic growth regulatory mechanisms governing breast cancer and controlling its malignant progres sion. In the two years since its publication, much new and exciting in formation has been published and the full interplay of regulatory mechanisms is now beginning to emerge. We have divided this book into four sections that we hope will unify important concepts and help to crystallize areas of consensus and/or disagreement among a diverse group of basic and clinical scientists working on the disease. The first section is devoted to studies on oncogenes, antioncogenes, proliferation, and tumor prognosis. The first chapter, by Sunderland and McGuire, introduces the characteristics of breast cancer as studied by patho logists to establish prognostic outcome. Of particular interest is a new proto oncogene called HER-2 (or neu), which is rapidly becoming accepted as a valuable new tumor marker of poor prognosis. The second chapter, by Lee Bookstein and Lee, introduces the best known antioncogene, the retinoblas toma antioncogene, whose expression is sometimes lost in breast cancer. Malignant progression appears to be influenced by the balance of proto oncogene and antioncogene expression.
Book Synopsis Regulation of Estrogen Receptor-alpha Mediated Gene Expression and Endocrine Resistance Through Estrogen Receptor-alpha Phosphorylation and Micro-RNA in Breast Cancer by : Kyuri Kim
Download or read book Regulation of Estrogen Receptor-alpha Mediated Gene Expression and Endocrine Resistance Through Estrogen Receptor-alpha Phosphorylation and Micro-RNA in Breast Cancer written by Kyuri Kim and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogens are associated with the development and progression of breast cancer in addition to their role in normal reproductive physiology, and estrogen receptors (ER) mediate the actions of estrogen in target tissues by regulating the expression of numerous biologically important target genes. The progression of human breast cancer and the development of resistance to endocrine therapies are thought to be associated with ER phosphorylation. We generated multiple combinations of ER phospho-mutants, at residues serine 104, 106, 118, 167, 236, and 305, and examined their impact on receptor half-life, the agonist and antagonist balance of selective estrogen receptor modulators (SERMs) and selective estrogen receptor downregulators (SERDs), the regulation of ER transcriptional activity, and stimulation of cell proliferation in response to estradiol and SERMs/SERD. We showed that changes in ER affecting the phosphorylation status of the receptor greatly impact receptor function and differential SERM and SERD modulated cellular responses that could contribute to resistance to endocrine therapies in breast cancer. We also studied the regulation of microRNAs (miRNAs) by estradiol and growth factors through ER and extracellular signal-regulated kinase 2 (ERK2) in order to understand their physiological impact on breast cancer. We identified nine miRNA- encoding genes harboring overlapping ER and ERK2 binding sites close to their transcription start sites, which require ER and ERK2 for transcriptional induction as well as estradiol- mediated miRNA regulation. We then identified TP63, a target of miR-101, miR-190 and miR- 196a2, and showed that TP63 plays an important role in estradiol- or growth factor-mediated cellular response in breast cancer cells (MCF-7 and MDA-MB-231) by increasing tumor cell growth and in vitro invasion mainly controlled by miR-196a2 action. These results suggest a tumor-suppressive role of miR-196a2 in regulating TP63 expression and the aggressive behavior of breast cancers.
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 Estrogen and Breast Cancer by : W. R. Miller
Download or read book Estrogen and Breast Cancer written by W. R. Miller and published by Landes Bioscience. This book was released on 1996 with total page 234 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Estrogen Receptor Gene Alterations in Human Breast Cancer by : Qiu-Xia Zhang
Download or read book Estrogen Receptor Gene Alterations in Human Breast Cancer written by Qiu-Xia Zhang and published by . This book was released on 1997 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Factors That Effect Signal Transduction by the Estrogen Receptor by :
Download or read book Factors That Effect Signal Transduction by the Estrogen Receptor written by and published by . This book was released on 1997 with total page 22 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of this proposal is to identify and characterize proteins involved in signaling by the estrogen receptor (ER), a transcription factor involved in many human breast tumors, using genetic strategies. Through dosage suppression analysis, we have isolated a gene that when overexpressed dramatically increases ER transcriptional activity. The gene is the yeast homologue of the human p23 protein, a component of the molecular chaperonin complex bound to many unliganded steroid receptors. The cellular distribution of p23 is mostly cytoplasmic, however, this pattern is altered upon expression of ER, whereupon p23 colocalizes with ER in the nucleus. This colocalization was seen in the absence of estrogen: addition of estrogen results in redistribution of p23 to the cytoplasm. Our work suggests that p23 is a positive regulator of ER, and therefore a possible means by which to control ER function and stop breast cancer growth.
Book Synopsis Identification and Characterization of Factors that Affect Estrogen Receptor Transcriptional Activation in Breast Cancer by :
Download or read book Identification and Characterization of Factors that Affect Estrogen Receptor Transcriptional Activation in Breast Cancer written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nearly half of human breast cancers are dependent on estrogen for growth. How estrogens stimulate cell growth is not understood. Estrogens activate an intracellular protein, the estrogen receptor (ER), which acts together with certain receptor-interacting proteins to "switch on" some genes involved in cellular proliferation. The goal of this%project is to identify and elucidate the roles of such receptor-interacting proteins in ER function. I have identified three proteins that interact with the ER using the yeast two-hybrid system, including the Vitamin D receptor-interacting protein 150 (DRIPl5O), subunit of a nuclear receptor coactivator complex. I am currently defining the effects of DRIPl5O on ER transcriptional activity using a transient transfection system designed to monitor ER- dependent transcriptional activation.
Book Synopsis Factors Modulating Estrogen Receptor Activity by :
Download or read book Factors Modulating Estrogen Receptor Activity written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The overall goal of our laboratory is to elucidate the mechanism of signal transduction and transcriptional regulation by the estrogen receptor (ER), a ligand- regulated transcription factor that plays a critical role in the development, progression and hormone responsiveness of breast cancer cells. Combining genetic, molecular and biochemical approaches, we have identified the Hsp9O-associated co-chaperone, p23, as a key regulator of ER action and have also determined that ER is phosphorylated and regulated by the cyclin A/Cdk2 complex. Understanding of the communication between ER and these regulator factors is fundamental to understanding the mechanism of ER- regulated gene expression and may reveal novel points of intervention to be exploited in the development of new therapies for breast cancer.
Book Synopsis Mechanisms of Transcriptional Activation of Estrogen Responsive Genes in Breast Cancer Cells by : Chien-Cheng Chen
Download or read book Mechanisms of Transcriptional Activation of Estrogen Responsive Genes in Breast Cancer Cells written by Chien-Cheng Chen and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogen receptor (ER) acts as a ligand-activated transcription factor that regulates the expression of genes. The genomic mechanisms of ER action include ligand-induced dimerization of ER which binds estrogen responsive elements (EREs) in the promoters of target genes. There are also nongenomic mechanisms of ER action which are associated with membrane bound or cytosol ER-dependent activation of various protein-kinase cascades which also influence expression of target genes. Egr-1 is an immediate-early gene induced by 17B-estradiol (E2) in the rodent uterus and breast cancer cells. Deletion analysis of the Egr-1 promoter identified a minimal E2-responsive region that contained serum response element (SRE3) which bound Elk-1 and serum response factor (SRF) in gel mobility shift assays. Hormone-responsiveness of Egr-1 in MCF-7 cells was specifically inhibited by PD98059, a MAPKK inhibitor, but not by LY294002, an inhibitor of PI3-K. These results contrasted with the hormone-dependent activation of the SRE in the c-fos promoter, which was inhibited by both PD98059 and LY294002, suggesting that Egr-1, like c-fos, is activated through non-genomic pathways of estrogen action but through activation of different kinases. COUP-TFs are orphan nuclear receptors expressed in a variety of tissues where they regulate biological functions and organogenesis. In this study, we investigated coactivation of ERa by COUP-TF1 in cell lines transiently cotransfected with the pERE3 construct. COUP-TFI coactivated ERał-mediated transactivation, but unlike many other coactivators, COUP-TFI also enhanced transactivation of ERa when cells were cotransfected with the TAF1-ERa mutant or the 19c-ERa mutant. These data indicate that helix 12 of ERa is not required for coactivation by COUP-TFI when AF-1 of ERa is intact. However, when the AF-1 of ERa is deleted, the intact AF-2 function is required for coactivation by COUP-TFI. Analysis of multiple COUP-TFI deletion mutants showed that the DNA-binding domain and C-terminal region of COUP-TFI were important for coactivation of ERa. Point mutations of the DNA-binding domain of COUP-TFI resulted in loss of interactions with ERa, suggesting that the DNA-binding domain of COUP-TFI is important for its coactivation activity facilitating interactions with ERa. These results demonstrate that COUP-TFI coactivated ERa through a non-classical LXXLL-independent pathway.
Book Synopsis Role of Estrogen Receptors in Estrogen and Xenoestrogens-induced Breast Cancer Cell Proliferation by : Michael Tsung-Ju Yang
Download or read book Role of Estrogen Receptors in Estrogen and Xenoestrogens-induced Breast Cancer Cell Proliferation written by Michael Tsung-Ju Yang and published by . This book was released on 1998 with total page 136 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Growth Factors and Oncogenes in Breast Cancer by : Mels Sluyser
Download or read book Growth Factors and Oncogenes in Breast Cancer written by Mels Sluyser and published by John Wiley & Sons. This book was released on 1987 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Estrogen Receptor Alpha Protein Interactions with Nuclear Components in Breast Cancer Cells by : Amy L. Weinberg
Download or read book Estrogen Receptor Alpha Protein Interactions with Nuclear Components in Breast Cancer Cells written by Amy L. Weinberg and published by . This book was released on 2007 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Dissecting the Role of Estrogen Receptor Palmitoylation in Breast Cancer Cells by :
Download or read book Dissecting the Role of Estrogen Receptor Palmitoylation in Breast Cancer Cells written by and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogen signaling is primarily mediated by two estrogen receptors (ERs), ER[alpha] and ER[beta]. ER[alpha] is expressed in ~70% of breast cancers and is an important diagnostic and therapeutic target. Developing better treatment options and overcoming limitations of endocrine therapy depend on a detailed understanding of ER[alpha]-signaling pathways. ER[alpha], a member of the class I nuclear receptor superfamily of transcription factors, localizes mainly to the nucleus and interacts with DNA regulatory sequences either directly or through interaction with other transcription factors to regulate gene transcription. ER[alpha] is also rapidly activates signaling cascades. S-palmitoylation, a reversible lipid modification is catalyzed by palmitoyl acyl-transferases (PAT), which increase affinity of proteins to the membrane. Based on the results of previous studies, it is hypothesized that palmitoylation of ER[alpha] regulates extranuclear and nuclear signaling of ER[alpha]. We utilized palmitoylation-defective mutant ER[alpha]C447A-expressing MDA-MB-468 breast cancer cells to dissect the role of palmitoylation in a breast cancer cell line model. The substitution of ER[alpha] palmitoylation site abrogated ER[alpha] palmitoylation, membrane localization and estrogen-dependent phosphorylation of ERK1/2 in MDA-MB-468 cell line. Besides loss of E2-dependent extranuclear signaling, the substitution of palmitoylation sites led to the loss of other ER[alpha]-dependent events in ER[alpha]C447A-expressing MDA-MB-468 cells, such as decreased E2-dependent S118 phosphorylation, impaired regulation of certain target genes, and loss of estrogen-dependent cell cycle inhibition. This study thus highlights the importance of ER[alpha] palmitoylation in both nuclear and extranuclear ER signaling pathways in breast cancer cells. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors.
Book Synopsis Estrogen Receptor Dependent Gene Regulation in Human Breast Cancer Cells by :
Download or read book Estrogen Receptor Dependent Gene Regulation in Human Breast Cancer Cells written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Activation of Estrogen Receptor Alpha, Aryl Hydrocarbon Receptor, and Nuclear Factor Erythroid-2 Like 2 in Human Breast Cancer Cells by : Raymond Ho Fai Lo
Download or read book Activation of Estrogen Receptor Alpha, Aryl Hydrocarbon Receptor, and Nuclear Factor Erythroid-2 Like 2 in Human Breast Cancer Cells written by Raymond Ho Fai Lo and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
