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
Abstract: The hormone testosterone plays crucial roles during male development and puberty and throughout life, as an anabolic regulator of muscle and bone structure and function. The actions of testosterone are mediated, primarily, through the androgen receptor, a member of the nuclear receptor superfamily. The androgen receptor gene is located on the X-chromosome and receptor levels are tightly controlled both at the level of transcription of the gene and post-translationally at the protein level. Sp1 has emerged as the major driver of expression of the androgen receptor gene, while auto-regulation by androgens is associated with both positive and negative regulation in a possible cell-selective manner. Research into the networks of positive and negative regulators of the androgen receptor gene are vital in order to understand the temporal and spatial control of receptor levels and the consequences for healthy aging and disease. A clear understanding of the multiple transcription factors participating in regulation of the androgen receptor gene will likely aid in the development and application of hormone therapies to boast or curb receptor activity. Highlights: The androgen receptor gene is X-linked and lacks a TATA-sequence in the promoter. Sp1 is a major driver for receptor mRNA expression. The 5′UTR contains several transcription factor binding sites mediating both positive and negative regulation. Androgens downs regulate receptor mRNA in breast and prostate cells but upregulate expression in bone.
Androgens play a critical role in the development and maintenance of the male reproductive system and affect important physiological processes and pathological conditions, including the homeostasis of the normal prostate and prostate cancer. Androgen Action: Methods and Protocols is designed to provide a tool box to study various phases of androgen action, from its entry to the cell to the phenotypic response that the cell mounts, with up-to-date techniques for biochemists, molecular biologists, cell biologists, geneticists, and pathologists. The volume opens with a brief review of the research history on androgen action and prostate carcinogenesis, followed by chapters that cover state-of-the-art methods to determine androgen levels in biological tissues and fluids, experimental procedures to study the various aspects of androgen receptor activity, and methodology to study salient examples of interactions between androgen signalling and other major signalling pathways in cells. Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Androgen Action: Methods and Protocols provides a comprehensive overview of, and practical guidance on, the diverse methodologies that are propelling androgen action research forward, both for normal physiology as well as in disease states.