Androgenic Effects of 11-Oxygenated Androgens in Castration-Resistant Prostate Cancer

Investigations of CRPC cell models demonstrate that both 11oxygenated androgens 11Ketotestesterone (11KT) and 11-hydroxytestosterone (11OHT) drive robust AR-mediated proliferative responses and significantly modulate gene and protein expression profiles, paralleling canonical androgens. They also exhibit unique transcriptional and post-transcriptional effects that include potential AR-independent pathways. Furthermore, the AR antagonist enzalutamide effectively inhibits their androgenic actions, suggesting they are primarily AR-mediated. Overall design: RNA-seq profiling of the prostate cancer cell lines DU145, LAPC4, VCaP exposed to R1881 or 11ketotestosterone or 11hydroxytestosterone with or without co-exposure to the androgen receptor inhibitor enzalutamide