Distinct transcriptional programs mediated by the ligand-dependent full-length androgen receptor and its splice variants in castration-resistant prostate cancer.

ABSTRACT: Continued androgen receptor (AR) signaling is an established mechanism underlying castration-resistant prostate cancer (CRPC), and suppression of androgen receptor signaling remains a therapeutic goal of CRPC therapy. Constitutively active androgen receptor splice variants (AR-Vs) lack the androgen receptor ligand-binding domain (AR-LBD), the intended target of androgen deprivation therapies including CRPC therapies such as abiraterone and MDV3100. While the canonical full-length androgen receptor (AR-FL) and AR-Vs are both increased in CRPCs, their expression regulation, associated transcriptional programs, and functional relationships have not been dissected. In this study, we show that suppression of ligand-mediated AR-FL signaling by targeting AR-LBD leads to increased AR-V expression

SUBMITTER: Hu R 

PROVIDER: S-EPMC3415705 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature