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Inhibition of SULT2B1b expression alters effects of 3β‐hydroxysteroids on cell proliferation and steroid hormone receptor expression in human LNCaP prostate cancer cells
Author(s) -
He Dongning,
Falany Charles N.
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20615
Subject(s) - lncap , endocrinology , medicine , androstenediol , cell growth , dehydroepiandrosterone , biology , small interfering rna , androgen , receptor , androgen receptor , sulfation , cell culture , transfection , chemistry , prostate , prostate cancer , hormone , cancer , biochemistry , genetics
Abstract BACKGROUND Sulfation is an important steroid inactivation in human tissues. Sulfotransferase (SULT) 2B1b selectively conjugates 3β‐hydroxysteroids and is expressed in epithelial cells of normal and cancerous prostate tissues. Dehydroepiandrosterone (DHEA) and Δ 5 ‐androstenediol (Δ 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, Δ 5 ‐Adiol, and 5α‐androstane‐3β‐17β‐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 Δ 5 ‐Adiol increased proliferation of control cells and the proliferative effects were significantly increased in SULT2B1b‐siRNA cells. DHEA, but not Δ 5 ‐Adiol increased AR levels at concentrations ≥1,000 nM in SULT2B1b‐siRNA cells but not in control LNCaP cells. ER‐α levels were not affected with any of the compounds tested. Physiological concentrations of DHEA and Δ 5 ‐A‐diol decreased ER‐β levels in control cells and had significantly greater effects in SULT2B1b‐siRNA cells. In contrast, Anstane‐diol had no effect on AR or ER‐α levels but induced more elevation of ER‐β levels in SULT2B1b‐siRNA cells at concentrations ≥1,000 nM. CONCLUSIONS SULT2B1b is involved in regulating prostate cell responsiveness to DHEA and Δ 5 ‐Adiol. Inhibition of SULT2B1b increased cell proliferation and ER‐β repression after treatment with physiological levels of DHEA and Δ 5 ‐Adiol indicating that SULT2B1b has an inhibitory effect on DHEA and Δ 5 ‐Adiol activity. Prostate 67: 1318–1329, 2007. © 2007 Wiley‐Liss, Inc.