Six transmembrane epithelial antigen of the prostate 1 is down-regulated by sex hormones in prostate cells

BACKGROUND STEAP1 is over-expressed in several types of tumors, especially prostate cancer, where it is localized in the plasma membrane of epithelial cells, at cellcell junctions. Its role in prostate carcinogenesis and its regulation in prostate cells remain unknown. Therefore, we propose to study the effect of sex hormones in the regulation of STEAP1 expression in prostate cells in vitro and in vivo. METHODS LNCaP prostate cells were incubated with fetal bovine serum (FBS), charcoal-stripped FBS (CS-FBS), 5-dihydrotestosterone (DHT), and 17-estradiol (E2) for different periods of stimulation. In addition, adult male Wistar rats were castrated and treated with DHT and E2. The levels of STEAP1 in response to treatments were analyzed by real-time PCR, Western blot, and immunohistochemistry. RESULTS The treatment of LNCaP cells with DHT or E2 induces a down-regulation of STEAP1 expression, while incubation with CS-FBS has the opposite effect. Experiments using inhibitors of androgen and estrogen receptor (AR and ER) showed that down-regulation of STEAP1 is AR-dependent, but ER-independent. However, the mediation of six transmembrane epithelial antigen of the prostate 1 (STEAP1) expression by AR seems to be dependent of de novo protein synthesis. In vivo studies showed that castrated rats express higher levels of STEAP1 protein when compared to intact rats, an effect reversed by DHT or E2 replacement. CONCLUSIONS STEAP1 is down-regulated by DHT and E2 in LNCaP cells and in rat prostate. Prostate 73: 605613, 2013. (c) 2012 Wiley Periodicals, Inc.