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 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.
CICS-UBI-Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, Covilhã, Portugal.
Inês M
IM
Gomes
Cecília R
CR
Santos
Sílvia
S
Socorro
Cláudio J
CJ
Maia
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000728:Androgens / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D045744:Cell Line, Tumor; D013196:Dihydrotestosterone / Q000378:metabolism* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009919:Orchiectomy; D010088:Oxidoreductases / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000728:Androgens; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004967:Estrogens; D009363:Neoplasm Proteins; C540293:STEAP1 protein, rat; D013196:Dihydrotestosterone; D004958:Estradiol; D010088:Oxidoreductases; C432763:STEAP1 protein, human