MP22-08 PROTEOSTASIS BY HSP70/STUB1 COMPLEX REGULATES ANDROGEN RECEPTOR VARIANTS EXPRESSION AND CONFERS RESISTANCE TO ENZALUTAMIDE AND ABIRATERONE

INTRODUCTION AND OBJECTIVES:Proteostasis is a complementary process by which cells control the protein biosynthesis, folding, trafficking and degradation. Evidence suggests that proteomic instability, such as protein misfolding and aggregation plays pivotal roles in cancer cell survival and progression. AR-V7 lacking the ligand binding domain confers resistance to enzalutamide and abiraterone in prostate cancer, targeting AR-V7 is an logical strategy to overcome the resistance. However, the mechanisms of AR-V7 proteostasis have not been fully studied so far. The objectives of this project are to investigate the roles of proteostasis in regulating AR-V7 expression and sensitivity to enzalutamide and abiraterone treatment.METHODS:Expression of HSP70 and STUB1 was determined by qRT-PCR and western blot. Expression of HSP70 and STUB1 was downregulated using specific siRNA. HSP70/STUB1 and AR-V7 interaction was determined by co-immunoprecipitation and dual immunofluorescence. The gene regulating mechanisms und...