Vitamin D - Metabolism in the Human Breast Cancer Cell Line MCF-7

Abstract

Background: The three main vitamin D metabolizing enzymes, vitamin D₃-25-hydroxylase (25-OHase, 25-hydroxylase), 25-hydroxyvitamin D₃-1α-hydroxylase (1α-OHase, 1α-hydroxylase) and 25-hydroxyvitamin D₃-24-hydroxylase (24-OHase, 24-hydroxylase), have been described in malignant breast tissue. This in vitro study aimed to obtain more information regarding the regulation of these enzymes in the human breast cancer cell line MCF-7. Materials and Methods: Vitamin D receptor (VDR)- positive MCF-7 cells in culture were stimulated with the vitamin D metabolites vitamin D₃, 25-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ for 24, 48; 72 and 96 hours in physiological and supraphysiological concentrations. The expressions of 25-hydroxylase, 1α-hydroxylase and 24-hydroxylase and their changes after stimulation were assessed by real-time PCR. Results: The expression of 25-hydroxylase was slightly influenced by vitamin D₃. The expression of 1α-hydroxylase was induced after stimulation with vitamin D₃ and 25-hydroxyvitamin D₃. Stimulation with 1,25-dihydroxyvitamin D₃ markedly increased the expression of 24-hydroxylase time- and dose-dependently. Conclusion: Our results demonstrated that MCF-7 cells are able to regulate the expression of 24-hydroxylase. This might be a mechanism for these tumor cells to protect themselves against the antiproliferative and apoptosis-inducing effects of calcitriol.