Inhibition of SULT2B1b expression alters effects of 3beta-hydroxysteroids on cell proliferation and steroid hormone receptor expression in human LNCaP prostate cancer cells.
BACKGROUND
Sulfation is an important steroid inactivation in human tissues. Sulfotransferase (SULT) 2B1b selectively conjugates 3beta-hydroxysteroids and is expressed in epithelial cells of normal and cancerous prostate tissues. Dehydroepiandrosterone (DHEA) and Delta(5)-androstenediol (Delta(5)-Adiol) sulfation prevents their conversion to more potent androgens and estrogens in tissues although both compounds may also be biologically active.


METHODS
SULT2B1b expression and activity were inhibited >85% in human LNCaP prostate adenocarcinoma cells using short interference RNA (siRNA). The effects of treating control and SULT2B1b-deficient LNCaP cells with DHEA, Delta(5)-Adiol, and 5alpha-androstane-3beta-17beta-diol (Anstane-diol) on cellular proliferation, estrogen receptors (ERs), androgen receptor (AR), and prostate specific antigen protein levels were examined.


RESULTS
Physiological concentrations of DHEA and Delta(5)-Adiol increased proliferation of control cells and the proliferative effects were significantly increased in SULT2B1b-siRNA cells. DHEA, but not Delta(5)-Adiol increased AR levels at concentrations >/=1,000 nM in SULT2B1b-siRNA cells but not in control LNCaP cells. ER-alpha levels were not affected with any of the compounds tested. Physiological concentrations of DHEA and Delta(5)-A-diol decreased ER-beta levels in control cells and had significantly greater effects in SULT2B1b-siRNA cells. In contrast, Anstane-diol had no effect on AR or ER-alpha levels but induced more elevation of ER-beta levels in SULT2B1b-siRNA cells at concentrations >/=1,000 nM.


CONCLUSIONS
SULT2B1b is involved in regulating prostate cell responsiveness to DHEA and Delta(5)-Adiol. Inhibition of SULT2B1b increased cell proliferation and ER-beta repression after treatment with physiological levels of DHEA and Delta(5)-Adiol indicating that SULT2B1b has an inhibitory effect on DHEA and Delta(5)-Adiol activity.
He
Dongning
D
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Falany
Charles N
CN
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000737:Androstenols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D011944:Receptors, Androgen / Q000096:biosynthesis; D011987:Receptors, Steroid / Q000096:biosynthesis*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C410798:AR protein, human; D000737:Androstenols; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D015238:Sulfotransferases; C433248:SULT2B1 protein, human; D017430:Prostate-Specific Antigen