Androgen and Anti-Androgen Treatment Modulates Androgen Receptor Activity and DJ-I Stability

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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.

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