The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen-receptor cofactors and bypass pathways

Edwards, J. and Bartlett, J.M.S. (2005) The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen-receptor cofactors and bypass pathways. BJU International, 95(9), pp. 1327-1335. (doi: 10.1111/j.1464-410X.2005.05527.x)

Abstract

Prostate cancer is the second leading cause of cancer related deaths in men from the western world. Treatment of prostate cancer has relied on androgen deprivation therapy for the past 50 years. Response rates are initially high (70-80%), however almost all patients develop androgen escape and subsequently die within 1-2 years. Unlike breast cancer, alternative approaches (chemotherapy and radiotherapy) do not increase survival time. The high rate of prostate cancer mortality is therefore strongly linked to both development of androgen escape and the lack of alternate therapies. AR mutations and amplifications can not explain all cases of androgen escape and post-translational modification of the AR has become an alternative theory. However recently it has been suggested that AR co-activators e.g. SRC-1 or pathways the bypass the AR (Ras/MAP kinase or PI3K/Akt) may stimulated prostate cancer progression independent of the AR. This review will focus on how AR coactivators may act to increase AR transactivation during sub-optimal DHT concentrations and also how signal transduction pathways may promote androgen escape via activation of transcription factors, e.g. AP-1, c-Myc and Myb, that induce cell proliferation or inhibit apoptosis.

• Item Type: Articles
• Additional Information: The definitive version is available at www.blackwell-synergy.com
• Keywords: Androgen receptor, hormone resistance, MAP kinase, PI3K, SRC-1, IL-6R, JAK and STAT3
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Edwards, Professor Joanne
• Authors: Edwards, J., and Bartlett, J.M.S.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: BJU International
• Journal Abbr.: BJU Int.
• Publisher: Wiley-Blackwell
• ISSN: 1464-4096
• ISSN (Online): 1464-410X
• Published Online: 12 May 2005
• Copyright Holders: Copyright © 2005 Wiley-Blackwell
• First Published: First published in British Journal of Urology International 95(9):1327-1335
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.