Analysis of the Vitamin D System in Cervical Carcinomas, Breast Cancer and Ovarian Cancer

Abstract

1,25-Dihydroxyvitamin D₃(1,(OH)₂D₃) is the biologically active metabolite of vitamin D and has been shown to regulate the growth of various cell types. There are two principal enzymes involved in the formation of circulating 1,(OH)₂D₃from vitamin D, the vitamin D 25-hydroxylase (25-OHase) and the 1a-hydroxylase (1α-OHase). Recently, extrarenal activity of 1a-OHase has been reported in various cell types. The aim of this study was to analyze expression of VDR and the main enzymes involved in the synthesis and metabolism of calcitriol in gynecological malignancies and corresponding normal tissue. Expression of VDR, 25-OHase, 1α-OHase, and 24-OHase was analyzed in breast carcinomas (BC), ovarian cancer (OC), cervix carcinomas (CC) and normal corresponding tissues using real-time PCR and specific hybridization probes as well as using immunohistochemistry. RNA for VDR, 1α-OHase, 24-OHase and 25-OHase was up-regulated in breast cervical and ovarian carcinomas as compared to normal tissue. VDR immunoreactivity was increased in breast and ovarian cancer and in cervix carcinomas as compared to normal corresponding tissue. Our findings indicate that cervical carcinomas, breast cancer and ovarian cancer may be considered as potential targets for prevention or therapy with new vitamin D analogs that exert little or no calcemic side effects or by pharmacological modulation of 1,(OH)₂D₃synthesis and metabolism in these tumor cells.