Bad expression influences time to androgen escape in prostate cancer

Teo, K., Gemmell, L., Mukherjee, R., Traynor, P. and Edwards, J. (2007) Bad expression influences time to androgen escape in prostate cancer. BJU International, 100(3), pp. 691-696. (doi: 10.1111/j.1464-410X.2007.07001.x)

Abstract

<b>OBJECTIVE</b>: To assess the role of selected downstream Bcl-2 family members (Bad, Bax, Bcl-2 and Bcl-xL) in the development of androgen-independent prostate cancer (AIPC), as androgen-deprivation therapy is the treatment of choice in advanced prostate cancer, yet patients generally relapse and progress to an AI state within 18–24 months. <b>PATIENTS, MATERIALS AND METHODS</b>: The patient cohort was established by retrospectively selecting patients with prostate cancer who had an initial response to androgen-deprivation therapy, but subsequently relapsed with AIPC. In all, 58 patients with prostate cancer were included with matched androgen-dependent (AD) and AI prostate tumours available for immunohistochemical analysis; two independent observers using a weighted-histoscore method scored the staining. Changes in Bad, Bax, Bcl-2 and Bcl-xL expression during transition to AIPC were evaluated and then correlated to known clinical variables. <b>RESULTS</b>: High Bad expression in AD tumours was associated with an increased time to biochemical relapse (<i>P</i> = 0.007) and a trend towards improved overall survival (<i>P</i> = 0.053). There were also trends towards a decrease in Bad (<i>P</i> = 0.068) and Bax (<i>P</i> = 0.055) expression with progression to AIPC. There were no significant results for Bcl-2 or Bcl-xL. <b>CONCLUSION</b>: There is evidence to suggest that Bad expression levels at diagnosis influence time to biochemical relapse and overall survival, and that levels of pro-apoptotic proteins Bad and Bax fall during AIPC development. Bad might therefore represent a possible positive prognostic marker and potential therapeutic target for AIPC in the future.

• Item Type: Articles
• Additional Information: The definitive version is available at www3.interscience.wiley.com
• Keywords: Bad, Bax, Bcl-2, Bcl-xL, prostate cancer
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Teo, Dr Katy and Edwards, Professor Joanne and McCall, Dr Pamela
• Authors: Teo, K., Gemmell, L., Mukherjee, R., Traynor, P., and Edwards, J.
• 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
• Publisher: Wiley-Blackwell
• ISSN: 1464-4096
• ISSN (Online): 1464-410X
• Published Online: 02 June 2007
• Copyright Holders: Copyright © 2007 Wiley-Blackwell
• First Published: First published in BJU International 100(3):691-696
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.