Role for a Steroid Sulfontransferase (SULT2B) in the Intratumoral Androgen Metabolism and in Prostate Cancer
Technical Report,29 Sep 2014,28 Sep 2015
Biomedical Research Foundation of South Texas SAN ANTONIO United States
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We are investigating the role of a steroid-metabolizing sulfotransferase SULT2B in intra-prostate androgen metabolism and in metastatic castration-resistant prostate cancer mCRPC stimulated by androgen-activated androgen receptor. SULT2B-mediated sulfation of dehydroepiandrosterone DHEA, the precursor steroid for the active androgen 5-dihydrotestosterone, should reduce intra-prostate DHEA levels, thereby inhibiting androgen production and stimulation of mCRPC by androgen receptor. We find that SULT2B is completely absent in distant metastases from mCRPC patients, suggesting a role for SULT2B in mCRPC. Causal association of SULT2B with mCRPC is indicated by our preliminary data, which show that xenograft tumors from SULT2B-knocked down CRPC cells grew faster than tumors from SULT2B-intact CRPC cells. In another notable result, CYP17A1 and HSD31, two key enzymes in the androgen biosynthesis pathway, were robustly induced in CRPC cells by androgen and vitamin D, respectively, and these inductions were prevented by co-treatment of cells with androgen and vitamin D. Concurrent presence of androgen also prevented vitamin D-mediated induction of CYP24A1, which converts1,25-dihydroxyD3 active vitamin D to an inactive metabolite. These results are potentially significant, suggesting that a combined vitamin D and androgen regimen may offer a novel therapy against mCRPC. Preclinical studies in mice are under way to test this possibility.