Androgen receptor mediates the expression of UDP‐glucuronosyltransferase 2 B15 and B17 genes

• DOI: 10.1002/pros.20749
• Publication Date: 2008-02-26T22:16:58Z
• Authors: Bo‐Ying Bao; Bin‐Fay Chuang; Qianben Wang; Oliver Sartor; Steven P. Balk; Myles Brown; Philip W. Kantoff; Gwo‐Shu Mary Lee
• Keywords: DU145; Dihydrotestosterone; Flutamide

Abstract BACKGROUND Enhanced androgen receptor (AR) activity by increased testosterone availability may play important roles in prostate cancer progressing to castration resistant state. Comparison of expression profiles dependent and independent tumors demonstrated a marked increase the UDP‐glucuronosyltransferase 2B15 (UGT2B15), an catabolic enzyme. We investigated mechanisms controlling differential UGT2B15 B17 response treatments. METHODS Gene was determined RT‐PCR. The association AR with UGT2B15/B17 genes Chromatin immuno‐precipitation (CHIP). RNA interference used knock‐down gene expression. RESULTS were not expressed negative cell lines, PC3 DU145, while they positive LNCaP, LNCaP‐abl (an LNCaP sub‐line), VCaP. levels up‐regulated comparing those LNCaP. These results suggest requirement for UGT2B15/B17. Treatment DHT down‐regulated time dose manner this down‐regulation competitively antagonized flutamide bicalutimide, suggesting pathway mediated AR. Further CHIP experiments direct interaction promoter regions genes. Knocking down significantly reduced completely inhibited DHT‐induced CONCLUSIONS that are primary androgen‐regulated is required both their basal Prostate 68:839–848, 2008. © 2008 Wiley‐Liss, Inc.