A1 Refereed original research article in a scientific journal
Androgen and anti-androgen treatment modulates androgen receptor activity and DJ-I stability
Authors: Pitkanen-Arsiola T, Tillman JE, Gu GY, Yuan JL, Roberts RL, Wantroba M, Coetzee GA, Cookson MS, Kasper S
Publisher: WILEY-LISS
Publication year: 2006
Journal: Prostate
Journal name in source: PROSTATE
Journal acronym: PROSTATE
Volume: 66
Issue: 11
First page : 1177
Last page: 1193
Number of pages: 17
ISSN: 0270-4137
DOI: https://doi.org/10.1002/pros.20450
Abstract
BACKGROUND. Mechanisms regulating the transition from hormone responsive to hormone refractory prostate cancer (PCa) have remained unclear.METHODS. We analyzed androgen and anti-androgen treatment on endogenous AR activity in primary human prostate epithelial (HPE) cells cultured directly from patient radical prostatectomy specimens utilizing a transiently infected gene reporter (TIGR) assay.RESULTS. Flutamide treatment exhibited agonist activities in HPE cells derived from tumor and non-tumor specimens which contained wild-type AR. After proteomic comparison of these cells to those where flutamide functioned normally as an antagonist, we identified DJ-1, a positive regulator of AR. DJ-1 expression increased in HPE and LNCaP cells during flutamide treatment as a result of DJ-1 protein stabilization.CONCLUSION. Stabilization of AR and its co-regulators in the absence of androgen may partially account for anti-androgen withdrawal syndrome and potentially contribute to the development of hormone refractory PCa.
BACKGROUND. Mechanisms regulating the transition from hormone responsive to hormone refractory prostate cancer (PCa) have remained unclear.METHODS. We analyzed androgen and anti-androgen treatment on endogenous AR activity in primary human prostate epithelial (HPE) cells cultured directly from patient radical prostatectomy specimens utilizing a transiently infected gene reporter (TIGR) assay.RESULTS. Flutamide treatment exhibited agonist activities in HPE cells derived from tumor and non-tumor specimens which contained wild-type AR. After proteomic comparison of these cells to those where flutamide functioned normally as an antagonist, we identified DJ-1, a positive regulator of AR. DJ-1 expression increased in HPE and LNCaP cells during flutamide treatment as a result of DJ-1 protein stabilization.CONCLUSION. Stabilization of AR and its co-regulators in the absence of androgen may partially account for anti-androgen withdrawal syndrome and potentially contribute to the development of hormone refractory PCa.
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