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Regulation Of The Estrogen Receptor And Its Coactivator Aib1 By Growth Factor Signaling
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Book Synopsis Regulation of the Estrogen Receptor and Its Coactivator, AIB1, by Growth Factor Signaling by : Jamie Nicole Holloway
Download or read book Regulation of the Estrogen Receptor and Its Coactivator, AIB1, by Growth Factor Signaling written by Jamie Nicole Holloway and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Regulation of the Activity of AIB1 an Estrogen Receptor Coactivator by Growth Factor Signals by :
Download or read book Regulation of the Activity of AIB1 an Estrogen Receptor Coactivator by Growth Factor Signals written by and published by . This book was released on 2003 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: The AIB1 protein is a member of a coactivator family that potentiates the transcriptional activity of the nuclear hormone receptors. AIB1, is amplified in certain breast and ovarian cancers and has been suggested that AIB1 plays a causative role in breast cancer development. Our lab recently identified AIB1 as a target of the MAPK signaling pathway (Font de Mora and Brown, Mol Cell Biol 20:5041, 2000). Based on these findings, we propose that the phosphorylation of AIB1 by MAPK may represent part of the molecular mechanism that integrates signals from steroid hormones and growth factors. In order to identify the sites of AIB1 that are phosphorylated by MAPK, seven potential phosphorylation sites were targeted for point mutations and or deletions. Previously we showed by an In vitro phosphorylation assay by (Erk2) that three out of the seven putative phosphorylation sites tested were most likely to be the specific MAPK phosphorylation sites. In order to investigate the physiological relevance of the AIB1 phosphorylation sites, we subcloned all mutants into GAL4DBD vector. We found that those mutants that showed low phosphorytation in vitro, gave the lowest transactivation levels when tested in vivo. In addition we were able to differentiate the sub-cellular localization of AIB1 after phosphorylation by performing transient transfection in COS cells using a constitutively active MAPK vector and a kinase inhibitor vector and further on performing immunofluorescence.
Book Synopsis Regulation of the Activity of AIB1, an Estrogen Coactivator, by Growth Factor Signals by :
Download or read book Regulation of the Activity of AIB1, an Estrogen Coactivator, by Growth Factor Signals written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: AIB1 is a member of a coactivator family that potentiates the transcriptional activity of nuclear hormone receptors. The AIB1 gene is amplified in certain breast and ovarian cancers. AIB1 amplification is preferentially found in ER and progesterone receptor-positive breast cancers. These findings suggest that AIB1 plays a causative role in breast cancer development. Our lab recently identified AIB1 as a target of the MAPK signaling pathway (Font de Mora and Brown, Mol Cell Biol 20:5041, 2000). This signaling pathway is triggered by growth factors of the insulin-like growth factor (IGF) and epidermal growth factor (EGF) family. These growth factors and their receptors have also been implicated in the development and progression of breast tumors. Based on these findings, we propose that the phosphorylation of AIB1 by MAPK may represent part of the molecular mechanism that integrates signals from steroid hormones and growth factors. Furthermore, we hypothesize that AIB1 phosphorylation may contribute to the role that AIB1 plays in the development of breast cancer. In order to identify the sites of AIB1 that are phosphorylated by MAPK, seven potential MAPK phosphorylation sites were targeted for deletion and mutations. In vitro phosphorylation of the point mutations and internal deletions by Erk2 revealed 4 major sites of phosphorylation. In the future we plan to test these mutants for their ability to function as coactivators. Our study will help to understand how AIB1 activity is modulated by MAPK. This may help to determine how AIB1 is involved in the development of breast cancer.
Book Synopsis EGF Regulation of Nuclear Co-Activator AIB1 Function in Breast Cancer by :
Download or read book EGF Regulation of Nuclear Co-Activator AIB1 Function in Breast Cancer written by and published by . This book was released on 2002 with total page 16 pages. Available in PDF, EPUB and Kindle. Book excerpt: Various growth factor receptor pathways promote human breast tumorigenesis of hormone-independent tumors. The nuclear receptor coactivator AIBi (amplified in breast cancer 1) can be phosphorylated and regulated by growth factor-induced signaling pathways such as MAP kinase and IkB kinase. Our lab has found a splice variant of AIBl, called delta exon3 AIBl, which has a higher co-activating ability than the full-length protein. This study determined the ability of delta exon3 splice variant compared with AIBi in potentiating growth factor signaling and to determine the mechanism of this potentiation using a growth factor responsive promoter.
Book Synopsis Endocrine Disruption and Human Health by : Philippa D. Darbre
Download or read book Endocrine Disruption and Human Health written by Philippa D. Darbre and published by Academic Press. This book was released on 2015-03-21 with total page 390 pages. Available in PDF, EPUB and Kindle. Book excerpt: Endocrine Disruption and Human Health starts with an overview of what endocrine disruptors are, the issues surrounding them, and the source of these chemicals in the ecosystem. This is followed by an overview of the mechanisms of action and assay systems. The third section includes chapters written by specialists on different aspects of concern for the effects of endocrine disruption on human health. Finally, the authors consider the risk assessment of endocrine disruptors and the pertinent regulation developed by the EU, the US FDA, as well as REACH and NGOs. The book has been written for researchers and research clinicians interested in learning about the actions of endocrine disruptors and current evidence justifying concerns for human health but is useful for those approaching the subject for the first time, graduate students, and advanced undergraduate students. - Provides readers with access to a range of information from the basic mechanisms and assays to cutting-edge research investigating concerns for human health - Presents a comprehensive, translational look at all aspects of endocrine disruption and its effects on human health - Offers guidance on the risk assessment of endocrine disruptors and current relevant regulatory considerations
Book Synopsis Activation of Estrogen Receptor-Beta-Dependent Transcription by Estrogen-Independent Pathways by :
Download or read book Activation of Estrogen Receptor-Beta-Dependent Transcription by Estrogen-Independent Pathways written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: There are two known receptors for estrogens, ERalpha and ERbeta The existence of ERbeta was only recently appreciated, and little is understood about its ability to be activated by intracellular signaling pathways in the absence of estrogens. The purpose of this research program is to characterize the ability of ERbeta to by activated by various ligand-independent signaling pathways, and to characterize the structural regions of ERbeta, in comparison to ERalpha, that regulate how this receptor isotype responds to intracellular cross-talk. We have found that stimulation of HeLa cells with forskolin and IBMX results in the activation of ERalpha and ERbeta dependent expression in a receptor-dependent and promoter context-dependent manner, and that protein kinase A mediates this response. Factors that interact with an AP-1 binding site contribute to forskolin/IBMX activation of estrogen receptor-dependent gene expression, and do so in a manner that does not require the A/B domain of either receptor. At least c-Jun is able to stimulate ERalpha activity via the AP-1 binding site. Multiple coactivator proteins, predominantly of the steroid receptor coactivator (SRC) family and CREB binding protein (CBP) can stimulate ERalpha and ERbeta activity induced by forskolin/lBMX pathways indicating that these coactivators can functionally interact with these receptors in the absence of ligand. Coactivation, however, does not appear to require SRC-1 phosphorylation as has been shown to be the case for progesterone receptors. This suggests that multiple pathways can be employed to regulate steroid receptor transcriptional pathways in a ligand-independent manner, and illustrates that understanding the mechanisms that control. ERalpha and ERbeta_transcription activity provides insight into how transcription factor cross-talk can be regulated by a single agent.
Book Synopsis Steroid Hormone Action by : Malcolm G. Parker
Download or read book Steroid Hormone Action written by Malcolm G. Parker and published by IRL Press. This book was released on 1993 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides a detailed overview of the mechanisms by which steroid hormones regulate gene activity in target cells. It should be of interest to molecular biologists, endocrinologists, pharmacologists and clinicians interested in gene regulation hormones and steroid antagonists.
Book Synopsis The Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis by :
Download or read book The Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis written by and published by . This book was released on 2008 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: AIBI (Amplified In Breast Cancer I) is a nuclear receptor coactivator whose gene is amplified in 5-10% of breast cancers and both the mRNA and protein are overexpressed in 30% of breast tumors. In vitro studies show that AIBI plays a significant role in estrogen and IGF-1-induced cell proliferation. Germline knockout of the AIBI gene leads to reduced somatic growth abnormal reproductive function and reduced mammary gland development. Knockout of AIBI expression also abrogates Ras-induced tumorigenesis. Furthermore patients with tumors expressing high levels of the growth factor HER2/Neu in addition to AIBI often develop anti-estrogen resistance to tamoxifen therapy. These findings imply that AIBI plays a fundamental role in the development of hormone-independent breast cancer through growth factor mediated pathways. Nonetheless the underlying mechanism of AIBI regulation of growth factor mediated mammary neoplasia is unknown. In this invesbgation I will utilize the MMTV-Neu mouse model (develop mammary gland tumors in 7-9 months) to elucidate the specific role of AIBI in growth factor-induced mammary tumorigenesis.
Book Synopsis Interaction of the DNA Bound Estrogen Receptor with Coregulatroy Proteins by : Varsha Sharad Likhite
Download or read book Interaction of the DNA Bound Estrogen Receptor with Coregulatroy Proteins written by Varsha Sharad Likhite and published by . This book was released on 2003 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 2017-10-23 with total page 678 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first of its kind, this reference gives a comprehensive but concise introduction to epigenetics before covering the many interactions between hormone regulation and epigenetics at all levels. The contents are very well structured with no overlaps between chapters, and each one features supplementary material for use in presentations. Throughout, major emphasis is placed on pathological conditions, aiming at the many physiologists and developmental biologists who are familiar with the importance and mechanisms of hormone regulation but have a limited background in epigenetics.
Book Synopsis An Investigation of Growth Factor Signaling Pathways Necessary for Estrogen Independent Growth and the Estrogen Receptor Alpha Negative Phenotype in Breast Cancer by : Michele K. Dougherty
Download or read book An Investigation of Growth Factor Signaling Pathways Necessary for Estrogen Independent Growth and the Estrogen Receptor Alpha Negative Phenotype in Breast Cancer written by Michele K. Dougherty and published by . This book was released on 2001 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Estrogen Receptor Alpha and the Regulation of Individual Differences in Maternal Care by : Sabine Dhir
Download or read book Estrogen Receptor Alpha and the Regulation of Individual Differences in Maternal Care written by Sabine Dhir and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The early life environment has a profound effect on offspring development. Extensive research has shown multiple neural, endocrine and behavioural systems are influenced by the quality of the early environment. In the laboratory rat, mother- pup interaction is a major component of the early life environment. Variations in the frequency of pup licking/grooming (LG) over the first week of life are associated with robust and stable differences in maternal care. Female rats will exhibit high levels of maternal behaviors towards their offspring when reared by mothers who display high levels of pup LG (High LG). The same is true for female offspring reared by dams that exhibit low levels of LG (Low LG). Adoption studies show that transmission of this maternal behaviour is non-genetic. The studies of the present thesis examine how maternal care, specifically pup LG, is passed from mother to daughter and the molecular mechanism that regulates this behaviour in High and Low LG female rats. High levels of maternal LG are associated with increased levels of the steroid hormone receptor estrogen receptor alpha (ER[alpha]) in the medial preoptic area (mPOA). This brain region is a key neural structure for the regulation of maternal behaviour. Our studies show that ER[alpha] in the mPOA is critically responsible for the variation in pup LG in High and Low LG dams. Furthermore, ER[alpha] also mediates the transmission of pup LG from mother to daughter. Examination of how ER[alpha] expression is regulated in the brain revealed increased Signal Transducer and Activator of Transcription 5b (Stat5b) transcription factor and RNA Polymerase II (RNA Pol II) binding to the ER[alpha] gene promoter in High LG compared to Low LG offspring. As well, chromatin immunoprecipitation (chIP) analysis revealed increased acetylation of lysine 9 on histone 3 (H3K9ac) in High LG offspring, suggesting that the ER[alpha] promoter is a more "open" chromatin state, and more conducive to increased gene transcription compared to Low LG offspring. Furthermore, increased pup LG significantly increases promoter binding of histone 3 lysine 9 tri-methylation and the associated histone methyltransferase, G9a, in High LG offspring. While seemingly counterintuitive, assessment of the binding of G9a to ER[alpha] via co-immunoprecipitation (co-IP) and to the ER[alpha] binding site via chIP analysis determined that G9a likely acts as a co-activator of ER[alpha]. Experimental knockdown of G9a in primary dissociated cortical cultured cells show that decreasing G9a is sufficient to decrease ER[alpha] expression levels. We also explored the dual methyltransferase/co-activation properties of G9a with a specific methyltransferase inhibitor, UNC0642 and found efficient inhibition of lysine 9 methylation on histone 3, with no alterations to G9a. Analysis of potential co-factor recruitment of Glucocorticoid Receptor Interacting Protein 1 (GRIP1) and Coactivator Associated Arginine Methyltransferase 1 (CARM1) by G9a to the ER[alpha] promoter suggests that G9a functions independently of other co-activators to increase ER[alpha] transcription in High LG offspring. The results of the present thesis extend our understanding of the molecular mechanism regulating variations in maternal care in High and Low LG offspring. In High LG offspring, increased pup LG is critically dependent on ER[alpha], which is dynamically regulated by a combination of increased transcription factor binding, permissive histone modifications, and increased co-activation by G9a. Taken together, these findings suggest how the effect of maternal LG on a specific molecular target can directly mediate the transmission of individual differences in maternal care." --
Book Synopsis Estrogens and Antiestrogens by : Robert Lindsay
Download or read book Estrogens and Antiestrogens written by Robert Lindsay and published by Lippincott Williams & Wilkins. This book was released on 1997 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis G Protein-Coupled Receptors in Energy Homeostasis and Obesity Pathogenesis by :
Download or read book G Protein-Coupled Receptors in Energy Homeostasis and Obesity Pathogenesis written by and published by Academic Press. This book was released on 2013-01-10 with total page 403 pages. Available in PDF, EPUB and Kindle. Book excerpt: Obesity is an epidemic with enormous health, economic and social burdens. Current drugs for obesity treatment are far from ideal in terms of efficacy and side effects. Reviews in this volume of Progress in Molecular Biology and Translational Science summarize current status in studies of a number of G protein-coupled receptors that were shown to be promising targets for obesity treatments. Some of these receptors also cause monogenic obesity in humans. - Subject matter: obesity is an epidemic and G protein-coupled receptors are promising drug targets, with significant potential as new anti-obesity drugs - Chapters are written by leading experts
Book Synopsis Nuclear Hormone Receptors by : Malcolm G. Parker
Download or read book Nuclear Hormone Receptors written by Malcolm G. Parker and published by . This book was released on 1991 with total page 434 pages. Available in PDF, EPUB and Kindle. Book excerpt: An overview of the supergene family made up of those nuclear hormone receptors which recognize thyroid and steroid hormones, vitamen D and retinoic acid and which are characterized by their ability to bind both ligands and the genes which respond to them.
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 Humana Press. This book was released on 2019-11-08 with total page 432 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 Steroid Hormones and Cell Cycle Regulation by : Kerry L. Burnstein
Download or read book Steroid Hormones and Cell Cycle Regulation written by Kerry L. Burnstein and published by Springer Science & Business Media. This book was released on 2002-05-31 with total page 290 pages. Available in PDF, EPUB and Kindle. Book excerpt: From the tissue culture dish to genetically modified mice, this volume explores the long recognized role of steroid hormones in regulating cell proliferation and differentiation. Many striking effects of steroid hormones are apparent during development and neoplasia and these topics are covered extensively. Several chapters address the pharmacological uses of steroid and related hormones, their analogs and antagonists in controlling growth of endocrine cancers. This book also highlights the complex role of cross talk between steroid hormones and signals initiated at the cell surface in the regulation of cell cycle in hormone responsive tissues.
