The Role of Steroid Receptor Coactivators (SRCs) in the Development of Prostate Cancer PDF Download

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Languages : en
Pages : 0

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In prostate cancer, androgen receptor (AR) supervises several key genes expressions. In the cell. AR exerts its regulatory control on a target cell only in the presence of its ligand, androgen. The regulatory functions of AR are more complex and are fine-tuned by accessory proteins. These proteins are required for the maximum biological impact by androgen. These modulators, called coactivators, provide a positive stimulus for receptor action. Our laboratory has cloned the first nuclear receptor coactivator SRC-1. SRC-1 and its related family members, SRC-2 and -3, have the capacity to activate the transcriptional activity of steroid receptor. However, the role of steroid receptor coactivators in prostate cancer is still unclear. To understand the function of these genes in the human prostate cancer, we have performed in situ hybridization on human prostate cancer, and generated SRC-3 overexpressing stable cell lines. During two years of this award, we have examined the SRC-3 is highly expressed in the prostate tumors and its expression is highly correlated with tumorigenesis by regulating the cell proliferation and cell growth.

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Languages : en
Pages : 31

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The hypothesis for this proposal is that in a substantial number of recurrent prostate cancers, growth is driven by the overexpression of steroid receptor coactivators SRC1 and TlF2 through their effects on AR-mediated gene expression. Completion of the studies proposed will elucidate the role of nuclear receptor coactivators in the progression of prostate cancer from the androgen-dependent to the recurrent state. We will test the hypothesis that recurrent prostate cancer growth is driven by the overexpression of coactivators SRCl and TIF2 through their effects on AR-mediated gene expression. By completing studies on coactivator expression in prostate cancer specimens, coactivator phosphorylation and the kinase signaling pathways responsible, we will establish a link between AR function as a part of the transcription complex and cell growth in recurrent prostate cancer.

Author: Gabriella Castoria
Publisher: Springer Science & Business Media
ISBN: 1461417643
Category : Medical
Languages : en
Pages : 271

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Breast and prostate cancers are both hormone-dependent, at least in some stages of their progression. Hormonal manipulation represents an important therapeutic approach. Although most of breast and prostate cancers initially respond to hormone therapy, most tumors reinitiate to growth. Finally, hormone-resistant and metastatic breast and prostate cancers may develop. Thus, the challenge is the dissection of mechanisms by which steroid receptor signaling pathways continue to influence cell growth and invasiveness. Compelling evidence indicates that steroid hormones elicit non-genomic responses in extra-nuclear compartment of target cells. In this cellular location, steroid-coupled receptors rapidly recruit signaling effectors or scaffold proteins and activate multiple pathways leading to proliferation, survival, migration and invasiveness. The immediate challenge is the dissection of key events regulating the steroid response of target tissues to prevent progression and improve treatment of breast and prostate cancers.

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Languages : en
Pages : 20

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E3 ubiquitin-protein ligase enzyme, E6-associated protein (E6-AP), is a novel dual function steroid hormone receptor coactivator. E6-AP not only interacts with and enhances the hormonedependent transcriptional activities of various steroid hormone receptors, including androgen receptor (AR), but also is a member of the E3 class of functionally related ubiquitin-protein ligases. Previously, using E6-AP knockout animals we have shown that E6-AP is required for the proper development and growth of prostate gland. Furthermore, we also show that protein levels of the components of phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt) signaling pathway are decreased in E6-AP knockout animals. In this report we show that over expression of E6-AP in the prostate gland leads to increased prostate gland size and also showed PIN like precancerous lesions. We also found that PI3K-Akt pathway is elevated in E6-AP transgenic prostate gland. In addition to that, stable LNCaP cells that stably overexpress exogenous E6-AP protein have elevated levels of PI3K, total Akt, phosphorylated Akt (active Akt) suggesting that E6-AP regulates the PI3K-Akt signaling pathway. This report also suggest that E6-AP may regulate PI3K-Akt signaling by regulating the protein levels of RhoA, a small GTPase, which is a negative regulator of the Akt signaling pathway via the ubiquitinproteasome pathway. In addition, we show that stable overexpression of E6-AP in prostate cancer cells results in decreased apoptosis. Overall our data suggests that E6-AP regulates the PI3K-Akt pathway in prostate cells which results in increased prostate gland growth, proliferation and decreased apoptosis.

Author: Malcolm G. Parker
Publisher: IRL Press
ISBN:
Category : Medical
Languages : en
Pages : 242

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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.

Author: Rakesh Kumar
Publisher: Springer Science & Business Media
ISBN: 1461480396
Category : Medical
Languages : en
Pages : 442

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At the moment, there is no dedicated book to summarize the roles, the significance, and potential therapeutic targeting of transcriptional factors from the perspective of signaling cascade, and thus, directly impacting the functionality of transcriptional factors in cancer. In addition, this book will offer a comprehensive basic and clinical science behind the functions of representative core transcriptional factors. These chapters will serve as a treasure for all those who have an interest in the basis, progression, and targeting of human cancer. Each chapter will be intended to provide comprehensive, up-to-date information by the leaders about the physiologic and pathologic roles of TFs in specific representative organ systems of prime importance. The book will consist of chapters that will give biomedical students, under and graduate students, basic sciences and clinical cancer fellows, residents and researchers, and oncology educators will get a thorough summary of the overall subject. The readers will be able to understand the important current information and views on specific TFs and its role in cancer in areas outside their own expertise or experience. A special emphasis will be also placed on the "classic" papers as well as perspectives on future directions for the field.

Author: Anne M. Etgen
Publisher: Academic Press
ISBN: 0080958583
Category : Psychology
Languages : en
Pages : 1100

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A single volume of 31 articles, Mechanisms of Hormone Actions on Behavior is an authoritative selection of relevant chapters from the Hormones Brain and Behavior 2e MRW, the most comprehensive source of neuroendocrinological information assembled to date (AP June 2009). The study of hormones as they impact the brain and, subsequently, behavior is a central topic in neuroscience, endocrinology and psychiatry. This volume offers an overview of neuroendocrinological topics, approaching the subject from the perspective of the mechanisms which control hormone actions on behavior. Female, male and stress hormones are discussed at the cellular, behavioral and developmental level, and sexual differentiation of the development of hormone-dependent neuronal systems, neuropeptides/neuromodulators, and steroid-inducedneuroplasticity are addressed. There is simply no other current single-volume reference with such comprehensive coverage and depth.Authors selected are the internationally renowned experts for the particular topics on which they write, and the volume is richly illustrated with over 175 figures (over 50 in color). A collection of articles reviewing our fundamental knowledge of the mechanisms of neuroendocrinology, the book provides an essential, affordable reference for researchers, clinicians and graduate students in the area. - The most comprehensive single-volume source of up-to-date data on the mechanisms behind neuroendocrinology, with review articles covering x,y z - Chapters synthesize information otherwise dispersed across a number of journal articles and book chapters, thus saving researchers the time consuming process of finding and integrating this information themselves - Offering outstanding scholarship, each chapter is written by an expert in the topic area and approximately 35% of chapters are written by international contributors - Provides more fully vetted expert knowledge than any existing work with broad appeal for the US, UK and Europe, accurately crediting the contributions to research in those regions - Heavily illustrated with 175 figures, approximately 54 in color - Presents material in most visually useful form for the reader

Author: Rogerio A. Lobo
Publisher: Elsevier
ISBN: 0080553095
Category : Technology & Engineering
Languages : en
Pages : 902

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For anyone who treats postmenopausal women, this latest edition of Rogerio Lobo's classic work combines the best from two well-known references: Menopause, and the second edition of Treatment of the Postmenopausal Woman. By adding significant discussions of the basic science behind menopause, it is possible to objectively assess the clinical value and limitations of current approaches to treatment and provide a basis and rationale for strategies that will result in better individualized and specialized care. Not only does the third edition discuss diagnosis and treatment of menopause but it covers biological, anatomical, physiological, pathobiological, and pharmacological aspects as well bringing together, in one source, all of the information needed to understand and treat postmenopausal conditions. Over 50% new material representing the vast amount of information available since the Women's Health Initiative (WHI) clinical trials were completed making this the most up-to-date reference on postmenopausal women Includes several new sections on comparisons between clinical trials and observational data, urology, and pelvic support Each section is preceded by a preface to put the area into context with many chapters having suggested treatment regimens

Author: Donald Tindall
Publisher: Springer Science & Business Media
ISBN: 0387691790
Category : Medical
Languages : en
Pages : 782

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Androgens are critical regulators of prostate differentiation and function, as well as prostate cancer growth and survival. Therefore, androgen ablation is the preferred systemic treatment for disseminated prostate cancer. Androgen action is exerted in target tissues via binding the androgen receptor (AR), a nuclear receptor transcription factor. Historically, the gene expression program mediated by the AR has been poorly understood. However, recent gene expression profiling and more traditional single-gene characterization studies have revealed many androgen-regulated genes that are important mediators of androgen action in both normal and malignant prostate tissue. This book will focus on the androgen-regulated gene expression program, and examine how recently identified androgen-regulated genes are likely to contribute to the development and progression of prostate cancer. Recent studies that have attempted to unravel how these genes are deregulated in androgen depletion independent prostate cancer will be included

Author: Albert Altchek
Publisher: Elsevier
ISBN: 008049451X
Category : Medical
Languages : en
Pages : 595

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This updated second edition of Diagnosis and Management of Ovarian Disorders provides thorough, yet succinct insight into the ever-changing realm of ovarian disorders. It presents a novel multidisciplinary approach to the subject as described by clinicians, surgeons, pathologists, basic scientists and related medical researchers. Topics covered include reproductive technology, early diagnosis of ovarian cancer, and management of menopause among others. The breadth of information provided by this book will appeal to clinicians and researchers involved in the study and treatment of ovarian disorders.KEY FEATURES* Includes updated information on early diagnosis of ovarian cancer* Reviews new diagnostic techniques for ovarian disorders* Discusses latest information on reproductive technology* Presents translational treatment linking laboratory research with clinical medicine