title: Vitamin D metabolism in mammary gland and breast cancer.
abstract: 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.
authors.affiliation: University at Albany Cancer Research Center, Rensselaer, NY 12144, USA. jwelsh@albany.edu
authors.forename: JoEllen
authors.initials: J
authors.lastname: Welsh
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002117:Calcitriol / Q000096:biosynthesis / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism*; D051379:Mice; D018167:Receptors, Calcitriol / Q000378:metabolism; D015398:Signal Transduction; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol