25-hydroxyvitamin D-1 alpha-hydroxylase (CYP27B1) is a new class of tumor suppressor in the prostate

The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)(2)D), inhibits proliferation and induces the differentiation of prostate cells in culture, attenuates tumor growth in animal models, and decreases prostate specific antigen (PSA) levels in prostate cancer patients. The enzymes that are responsible for the activation of vitamin D to 1 alpha,25(OH)(2)D include vitamin D-25-hydroxylase (25-OHase) and 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-OHase or CYP27B1) and are present in cultured prostate cells. The demonstration that a differential expression of 1 alpha-OHase between noncarcinogenic and carcinogenic prostate cells and the ability of epidermal growth factor (EGF) to up-regulate 1 alpha-OHase promoter activity in the noncarcinogenic, not the carcinogenic prostate cells suggested that a dysregulation of 1 alpha-OHase in cancer cells may lead to the aberrant growth of prostate cancer cells. Thus, the 1 alpha-OHase gene is a tumor suppressor gene responsible for the normal regulation of prostate cell growth.