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Function of an Androgen Receptor Coactivator Regulated in Prostate Development and Prostate Cancer

Function of an Androgen Receptor Coactivator Regulated in Prostate Development and Prostate Cancer PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 11

Book Description
We hypothesize that ART-27 affects AR-dependent differentiation of prostate epithelial cells by regulating a subset of AR responsive genes important to prostate growth suppression and differentiation. We further hypothesize that alterations in the level of ART-27 modulates AR activity, which, in turn, affects AR-dependent cell growth regulation in vivo. Our aims are to identify ART-27-dependent AR-target genes involved in growth suppression and differentiation and to elucidate the mechanism of regulation of ART-27 expression in prostate cancer. Our approach is to ablate ART-27 protein using siRNA technology followed by gene expression array. Our preliminary findings indicate that loss of ART-27 may result in enhanced expression of genes that are often over-expressed in prostate cancer such as PSA, FKBP5, SOR, KRT18, and CDKN3. Loss of ART-27 also shows enhanced expression of at least one positive regulator of tumor growth, CDKN3.

Function of an Androgen Receptor Coactivator Regulated in Prostate Development and Prostate Cancer

Function of an Androgen Receptor Coactivator Regulated in Prostate Development and Prostate Cancer PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 11

Book Description
We hypothesize that ART-27 affects AR-dependent differentiation of prostate epithelial cells by regulating a subset of AR responsive genes important to prostate growth suppression and differentiation. We further hypothesize that alterations in the level of ART-27 modulates AR activity, which, in turn, affects AR-dependent cell growth regulation in vivo. Our aims are to identify ART-27-dependent AR-target genes involved in growth suppression and differentiation and to elucidate the mechanism of regulation of ART-27 expression in prostate cancer. Our approach is to ablate ART-27 protein using siRNA technology followed by gene expression array. Our preliminary findings indicate that loss of ART-27 may result in enhanced expression of genes that are often over-expressed in prostate cancer such as PSA, FKBP5, SOR, KRT18, and CDKN3. Loss of ART-27 also shows enhanced expression of at least one positive regulator of tumor growth, CDKN3.

Androgen Action in Prostate Cancer

Androgen Action in Prostate Cancer PDF Author: Donald Tindall
Publisher: Springer Science & Business Media
ISBN: 0387691790
Category : Medical
Languages : en
Pages : 782

Book Description
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

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

The Role of Steroid Receptor Coactivators (SRCs) in the Development of Prostate Cancer PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

Book Description
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.

Role of ART-27, a Novel Androgen Receptor Coactivator, in Normal Prostate and Prostate Cancer

Role of ART-27, a Novel Androgen Receptor Coactivator, in Normal Prostate and Prostate Cancer PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

Book Description
The Androgen receptor (AR) is a hormone-dependent transcription factor involved in the regulation of both normal and malignant prostate cell growth. However, the precise mechanisms by which AR regulates normal prostate development and initiates prostate cancer have yet to be elucidated. It is believed that co-factors (coactivators and corepressors) that interact with the AR and modulate its activity play an important role in these processes. ART-27, as a newly identified AR coactivator, its function in normal prostate development and prostate cancer need yet to be elucidated. Modulation ART-27 levels in vivo such as knocking out ART-27 in the mouse will be our ultimate answer to these questions. Meanwhile recent studies have suggested that ART-27 may confer AR-dependent growth suppression and differentiation, if so, any alteration in ART27:AR interaction with those N-terminal mutated AR identified in some prostate cancer patients, will provide important genetic evidence for the role of ART27 in human disease, such as prostate cancer.

Androgen-Responsive Genes in Prostate Cancer

Androgen-Responsive Genes in Prostate Cancer PDF Author: Zhou Wang
Publisher: Springer Science & Business Media
ISBN: 1461461820
Category : Medical
Languages : en
Pages : 347

Book Description
Androgens and androgen receptors (AR) play critical roles in the development and progression of prostate cancer, the most frequently diagnosed cancer and second leading cause of cancer death in US males. AR is an androgen-dependent DNA-binding transcription factor that regulates the expression of androgen-responsive genes. Identification and characterization of androgen-responsive genes provide insights into the cellular mechanisms of androgen action and may lead to new approaches in diagnosis, prognosis, prevention and/or treatment of prostate cancer. This volume provides critical information from well respected experts in the field. Some of the exciting topics include the new understanding of mechanisms underlining the regulation of androgen-responsive gene expression, and functions of various androgen-responsive genes in biological processes essential in carcinogenesis including cell growth, angiogenesis, and epithelial-to-mesenchyme transition (EMT). Other important aspects addressed are the current and potential clinic applications of knowledge on androgen-responsive gene regulation and function. This book is intended for researchers, scientists, faculty, and advanced graduate students with an interest in androgen action and prostate cancer.​

Molecular Biology of Prostate Cancer

Molecular Biology of Prostate Cancer PDF Author: Manfred Wirth
Publisher: Walter de Gruyter
ISBN: 3110807270
Category : Medical
Languages : en
Pages : 220

Book Description


Endocrinology of the Testis and Male Reproduction

Endocrinology of the Testis and Male Reproduction PDF Author: Manuela Simoni
Publisher: Springer
ISBN: 9783319444406
Category : Medical
Languages : en
Pages : 1364

Book Description
This book provides a comprehensive overview of endocrinology of the male reproductive system, explaining how it works and how, sometimes, it fails to work. World-class specialists present state of the art knowledge on all aspects, including anatomy, physiology, molecular biology, genetics, pathophysiology, clinical manifestations of testicular diseases, endocrine aspects of andrological and sexual diseases, and therapy. Extensive consideration is given to sexual development, testicular function, the clinical approach to disorders of male reproduction, male hypogonadism, sexual dysfunction, and male infertility. In addition, sociodemographic, psychological, and ethical aspects of male reproductive disorders are discussed. The book is intended as a major reference for endocrinologists, andrologists, and sexologists, as well as basic and clinical scientists. It is published as part of the SpringerReference program, which delivers access to living editions constantly updated through a dynamic peer-review publishing process.

Androgen Action in Prostate Cancer

Androgen Action in Prostate Cancer PDF Author: Donald J. Tindall
Publisher: Springer
ISBN: 9780387691770
Category : Medical
Languages : en
Pages : 826

Book Description
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

Prostate Cancer

Prostate Cancer PDF Author: Scott M. Dehm
Publisher: Springer Nature
ISBN: 303032656X
Category : Medical
Languages : en
Pages : 483

Book Description
The purpose of this book is to provide a contemporary overview of the causes and consequences of prostate cancer from a cellular and genetic perspective. Written by experts in the fields of epidemiology, toxicology, cell biology, genetics, genomics, cell-cell interactions, cell signaling, hormone signaling, and transcriptional regulation, the text covers aspects of prostate cancer from disease initiation to metastasis. Chapters explore in depth the cells of origin for prostate cancer, its genomic subtypes, neural transcription factors in disease progression, epigenetic regulation of chromatin, and many other topics. This book distinguishes itself from other texts on prostate cancer by its focus on cellular and genetic mechanisms, as opposed to clinical diagnosis and management. As a result, this book will be of broad interest to basic and translational scientists with familiarity of these topics, as well as to trainees at earlier stages of their research careers.

Mechanism and Regulation of Gene Expression by Androgen Receptor in Prostate Cancer

Mechanism and Regulation of Gene Expression by Androgen Receptor in Prostate Cancer PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

Book Description
Our general objective is to use completely defined cell-free transcription systems both to identify novel AR-associated cofactors and to investigate the mechanism of action of AR and both novel and previously identified candidate coactivators. To this end, we have expressed and purified 5 AR-associated cofactors and established a chromatin assembly system to study AR function with chromatin template. We have shown an enhancement of AR function by the TRAP/Mediator coactivator complex that is generally utilized by a number of different nuclear receptors. Relevant to the mechanism involved, we have identified two TRAP/Mediator subunits as potential targets for the liganded AR receptor. The expression of AR and 10 cofactors by quantitative in situ RNA hybridization in 44 primary prostate cancers with different degree of differentiation was investigated. Our results revealed near constant expression of AR and heterogeneous expression of AR cofactors. Expression of PIAS1 and Ran/ARA24 was increased and expression of ELEl/ATRA70 was decreased. In addition, we demonstrated that the human prostate tumor cell proliferation and colony formation are markedly reduced by over-expression of ELEl/ARA70. Together, these findings indicate that the change of expression levels of AR cofactors may play important roles in prostate growth and tumorigenesis.