Molecular cloning and functional study of rat estrogen receptor-related receptor γ in rat prostatic cells

BACKGROUND. Based on high homology of ERRs with ERs, we hypothesize that ERRs might functionally cross talk with ERs or independently in prostatic cells. METHODS. We examined the ERR gamma expressions in rat prostates and Nb rat prostate cancer model, and its growth regulation in stable transfectants of prostatic cells. RESULTS. We cloned the ERR gamma cDNA from rat prostate by RACE-PCR. Its expression was confirmed by Northern and immunoblottings. Real-time RT-PCR showed that its expression in castrated prostates was androgen-dependent. ERR gamma was expressed in prostatic epithelial cells, but showed reduced expressions in neoplastic prostates. Transfections confirmed that ERR gamma was expressed in prostatic cells as nuclear protein and transcriptionally active without estradiol. Its overexpression in ERR gamma-stable transfectants of NbE-1 and MAT-Lu cells inhibited their in vitro proliferation, anchorage-independent growth in soft-agar and tumorigenicity in nude mice. CONCLUSIONS. Our studies show that ERR gamma is functionally expressed in rat prostate and may play anti-proliferative actions in prostatic cells. Its co-expression with ERs suggests that besides ERs, ligand-independent ERR gamma is also involved in prostatic growth and functions.