MP22-05 AKR1C3 PROMOTES AR-V7 PROTEIN STABILIZATION AND CONFERS ANTI-ANDROGEN RESISTANCE IN ADVANCED PROSTATE CANCER

INTRODUCTION AND OBJECTIVES:The resistant mechanisms of next generation anti-androgens in castration resistant prostate cancer are incompletely understood. Our previous work demonstrated that AKR1C3 and AR-V7 play important roles in enzalutamide and abiraterone resistance, and that targeting AKR1C3 or AR-V7 could overcome this resistance. The aim of this study is to investigate the interaction between AKR1C3 and AR-V7 and determine their coordinated roles in drug resistance.METHODS:Global gene expression analysis was analyzed by microarray analysis. Steroid profile including androgens in tumor tissues was analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). The effects of AKR1C3 expression and activation were examined by knockdown of AKR1C3 expression using lentiviral shRNA or inhibition of AKR1C3 enzymatic activity by indomethacin. AKR1C3 and AR-V7 interaction were determined by co-immunoprecipitation and dual immunofluorescence. The effects of AKR1C3 activation on anti-androgen sensitivity were ...