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BACKGROUND Regucalcin (RGN) is a calcium (Ca2+)-binding protein underexpressed in prostate adenocarcinoma comparatively to non-neoplastic prostate or benign prostate hyperplasia cases. Moreover, RGN expression is negatively associated with the cellular differentiation of prostate adenocarcinoma, suggesting that loss of RGN may be associated with tumor onset and progression. However, the RGN actions over the control of prostate cell growth have not been investigated. METHODS Androgens are implicated in the promotion of prostate cell proliferation, thus we studied the in vivo effect of androgens on RGN expression in rat prostate. The role of RGN modulating cell proliferation and apoptotic pathways in rat prostate was investigated using transgenic animals (Tg-RGN) overexpressing the protein. RESULTS In vivo stimulation with 5α-dihydrotestosterone (DHT) down-regulated RGN expression in rat prostate. Cell proliferation index and prostate weight were reduced in Tg-RGN, which was concomitant with altered expression of cell-cycle regulators. Tg-RGN presented diminished expression of the oncogene H-ras and increased expression of cell-cycle inhibitor p21. Levels of anti-apoptotic Bcl-2, as well as the Bcl-2/Bax protein ratio were increased in prostates overexpressing RGN. Both caspase-3 expression and enzyme activity were decreased in the prostates of Tg-RGN. CONCLUSIONS Overexpression of RGN resulted in inhibition of cell proliferation and apoptotic pathways, which demonstrated its role maintaining prostate growth balance. Thus, deregulation of RGN expression may be an important event favoring the development of prostate cancer. Moreover, the DHT effect down-regulating RGN expression in rat prostate highlighted for the importance of this protein in prostatic physiology. Prostate 74:1189–1198, 2014. © 2014 Wiley Periodicals, Inc.

Regucalcin (RGN) is a calcium (Ca(2+) )-binding protein underexpressed in prostate adenocarcinoma comparatively to non-neoplastic prostate or benign prostate hyperplasia cases. Moreover, RGN expression is negatively associated with the cellular differentiation of prostate adenocarcinoma, suggesting that loss of RGN may be associated with tumor onset and progression. However, the RGN actions over the control of prostate cell growth have not been investigated.Androgens are implicated in the promotion of prostate cell proliferation, thus we studied the in vivo effect of androgens on RGN expression in rat prostate. The role of RGN modulating cell proliferation and apoptotic pathways in rat prostate was investigated using transgenic animals (Tg-RGN) overexpressing the protein.In vivo stimulation with 5α-dihydrotestosterone (DHT) down-regulated RGN expression in rat prostate. Cell proliferation index and prostate weight were reduced in Tg-RGN, which was concomitant with altered expression of cell-cycle regulators. Tg-RGN presented diminished expression of the oncogene H-ras and increased expression of cell-cycle inhibitor p21. Levels of anti-apoptotic Bcl-2, as well as the Bcl-2/Bax protein ratio were increased in prostates overexpressing RGN. Both caspase-3 expression and enzyme activity were decreased in the prostates of Tg-RGN.Overexpression of RGN resulted in inhibition of cell proliferation and apoptotic pathways, which demonstrated its role maintaining prostate growth balance. Thus, deregulation of RGN expression may be an important event favoring the development of prostate cancer. Moreover, the DHT effect down-regulating RGN expression in rat prostate highlighted for the importance of this protein in prostatic physiology.

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 cell–cell 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), 5α-dihydrotestosterone (DHT), and 17β-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: 605–613, 2013. © 2012 Wiley Periodicals, Inc.