Steroidogenic factor 1 promotes aggressive growth of castration-resistant prostate cancer cells by stimulating steroid synthesis and cell proliferation.

摘要: The dependence of prostate cancer on androgens provides a targeted means treating advanced disease. Unfortunately, androgen deprivation therapies eventually become ineffective, leading to deadly castration-resistant (CRPC). One many factors implicated in the transition CRPC is onset de novo steroidogenesis. Although reactivation steroid receptors likely plays pivotal role aggressive CRPC, little understood regarding mechanisms whereby cells initiate and maintain We hypothesize that steroidogenic factor 1 (SF1, NR5A1, AD4BP), key regulator steroidogenesis normal endocrine tissues, expressed where it stimulates aberrant fuels growth. Notably, SF1 not tissue. Our results indicated was absent benign but present cell lines. Introduction ectopic expression human epithelial (BPH-1) stimulated increased enzyme expression, synthesis, proliferation. In contrast, data from an line (BCaPT10) demonstrated required for steroid-mediated growth because BCaPT10 diminished by abiraterone treatment short hairpin RNA-mediated knockdown (shSF1). SF1-depleted also exhibited defective centrosome homeostasis. Finally, whereas xenograft experiments castrated hosts with control transplants grew large, invasive tumors, BCaPT10-shSF1 failed grow. Therefore, we conclude accumulation controls homeostasis mediate within castrate environment. These findings new molecular mechanism therapeutic target CRPC.