Vitamin D metabolism in mammary gland and breast cancer

1α,25-Dihydroxycholecalciferol (1,25D) mediates growth inhibition and terminal differentiation in mammary epithelial cells via interaction with the vitamin D receptor (VDR). This review focuses on the concept that cells in the mammary gland express the vitamin D metabolizing enzyme CYP27B1 which converts the circulating vitamin D metabolite 25D to the active metabolite 1,25D. In support of this concept, CYP27B1 is developmentally regulated in mouse mammary gland, with highest levels found during pregnancy and lactation. In addition, human mammary cells cultured from normal breast tissue express VDR, CYP27B1 and the megalin–cubilin complex that facilitates internalization of 25D complexed with the vitamin D binding protein. When incubated with physiological concentrations of 25D, human mammary cells synthesize 1,25D in sufficient quantities to mediate growth inhibition. However, emerging evidence suggests that deregulation of VDR and CYP27B1 occurs during cancer development and contributes to abrogation of the tumor suppressive effects triggered by 25D.

► Mammary epithelial cells express vitamin D receptor and the vitamin D metabolizing enzyme CYP27B1. ► Expression of the vitamin D receptor and CYP27B1 is developmentally regulated in murine mammary gland. ► CYP27B1 catalyzes synthesis of 1,25-dihydroxycholecalciferol, the vitamin D receptor ligand, in human mammary cells. ► Oncogenes and tumor suppressors reduce expression and function of the vitamin D receptor and vitamin D metabolizing enzymes.