Glucocorticoid Receptor is distinct from Androgen Receptor function in Castrate-Resistant Prostate Cancer

Commonly used therapies for prostate cancer (PC) that block androgen receptor (AR) signaling inhibit regrowth, but aggressive castrate-resistant (CR)PC abrogates anti-androgen therapy. Recently published data shows that glucocorticoid receptor (GR) can drive the growth of CRPC when AR is blocked, by mimicking AR activity. Due to the evolution of CRPC into a more invasive disease, we hypothesized that GR-driven CRPC has different activities than AR that promote progression to metastatic disease. To test this hypothesis, we performed gene expression analysis on available datasets to determine which pathways correlate with GR target gene expression. Furthermore, we investigated gene expression in CWR-22Rv1 CRPC cells via qRT-PCR. Our results show that GR-activation in AR-blocked cells induces different genes than AR, suggesting that GR-driven CRPC is unique from AR-driven disease. The scientific contribution of our research may reveal new mechanisms by which GR drives PC progression and unveil novel therapeutic targets.