Androgen Action in Prostate Cancer (eBook)

Donald Tindall, James Mohler (Herausgeber)

eBook Download: PDF
2009 | 2009
VIII, 826 Seiten
Springer New York (Verlag)
978-0-387-69179-4 (ISBN)

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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


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

Contents 5
Introduction: Proper Nomenclature Facilitates Clinical and Translational Research in Prostate Cancer 9
Part I: The Role of Androgens in Developement of the Normal Prostate and Progression of Prostate Cancer 14
Androgen Action and Modulation of Prostate and Prostate Cancer Growth: An Historical Perspective 15
Clinical Progression to Castration-Recurrent Prostate Cancer 62
Differential Roles of Androgen Receptor in Prostate Development and Cancer Progression 78
Imaging Androgen Receptor Function In Vivo 95
Part II: Androgen Metabolism 125
Increased Expression of Genes Converting Adrenal Androgens to Testosterone in Castration-Recurrent Prostate Cancer 126
Androgen-Metabolic Genes in Prostate Cancer Predisposition and Progression 143
Effect of Steroid 5a-Reductase Inhibitors on Markers of Tumor Regression and Proliferation in Prostate Cancer 157
5a-Reductase Isozymes in Castration-Recurrent Prostate Cancer 176
Improving Intermittent Androgen-Deprivation Therapy: OFF Cycle and the Role of Steroid 5a-Reductase Inhibitors 187
Part III: Androgen Receptor Structure/Function Relationships 205
Insights from AR Gene Mutations 206
Functional Motifs of the Androgen Receptor 240
The Role of the Androgen Receptor Polyglutamine Tract in Prostate Cancer: In Mice and Men 267
The Androgen Receptor Coactivator-Binding Interface 294
Part IV: Co-Regulators of the Androgen Receptor 309
Coregulators and the Regulation of Androgen Receptor Action in Prostate Cancer 310
Androgen Receptor Coregulators and Their Role in Prostate Cancer 336
Interaction of the Androgen Receptor Ligand-Binding Domain with the N-Terminal Domain and with Coactivators 370
Multitasking and Interplay Between the Androgen Receptor Domains 380
Chromatin Remodeling and Androgen Receptor-Mediated Transcription 400
Part V: Ligand-Independent Activation of the Androgen Receptor 420
Ligand-Independent Androgen Receptor Activity 421
Role of IL-6 in Regulating the Androgen Receptor 444
The Role of Cyclic AMP in Regulating the Androgen Receptor 457
Part VI: Role of the Androgen Receptor in Prostate Cancer During Castration 496
Cellular and Molecular Signatures of Androgen Ablation of Prostate Cancer 497
Tissue Levels of Androgens in Castration-Recurrent Prostate Cancer 542
Unique Effects of Wnt Signaling on Prostate Cancer Cells: Modulation of the Androgen Signaling Pathway by Interactions of the Androgen Receptor Gene and Protein with Key Components of the Canonical Wnt Signaling Pathway 558
The Role of Foxa Proteins in the Regulation of Androgen Receptor Activity 576
Part VII: Androgen-Regulated Genes during Prostate Cancer Progression 605
Androgen Receptor as a Licensing Factor for DNA Replication 606
Androgen-Regulated Genes in the Prostate 618
Mapping the Androgen Receptor Cistrome 649
Differential Regulation of Clusterin Isoforms by the Androgen Receptor 667
Androgen Regulation of Prostate Cancer Gene Fusions 687
Androgens and the Lipogenic Switch in Prostate Cancer 708
Part VIII: The Androgen Receptor as a Drugable Target 725
Molecular Biology of Novel Targets Identified Through Study of Castration-Recurrent Prostate Cancer 726
Selenium and Androgen Receptor in Prostate Cancer 738
Index 764

Erscheint lt. Verlag 20.4.2009
Zusatzinfo VIII, 826 p.
Verlagsort New York
Sprache englisch
Themenwelt Medizin / Pharmazie Medizinische Fachgebiete Mikrobiologie / Infektologie / Reisemedizin
Medizin / Pharmazie Medizinische Fachgebiete Onkologie
Medizin / Pharmazie Medizinische Fachgebiete Pharmakologie / Pharmakotherapie
Studium 2. Studienabschnitt (Klinik) Humangenetik
Studium Querschnittsbereiche Infektiologie / Immunologie
Naturwissenschaften Biologie Mikrobiologie / Immunologie
Technik
Schlagworte DNA • Drogen • gene expression • genes • Imaging • transcription
ISBN-10 0-387-69179-0 / 0387691790
ISBN-13 978-0-387-69179-4 / 9780387691794
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