Role of Apoptosis in the Growth Inhibitory Effects of Vitamin D in MCF-7 Cells
1,25-dihydroxycholecalciferol (1,25(OH)2D3) is the biologically active form of vitamin D, a fat soluble vitamin originally identified as an anti-rachitic factor in the early 1920s. Since that discovery, the molecular pathways by which 1,25(OH)2D3 functions to maintain calcium homeostasis and bone turnover have been intensely investigated. 1,25(OH)2D3 interacts with the vitamin D receptor, which is a member of the steroid/thyroid/retinoic acid superfamily of nuclear receptors, and induces or represses expression of specific genes whose protein products mediate the biological responses attributed to vitamin D. Vitamin D modulated proteins include calcium binding proteins (calbindins D9K, D28K), bone matrix proteins (osteocalcin, osteopontin), digestive enzymes (alkaline phosphatase) and vitamin D metabolizing enzymes (24-hydroxylase). The expression of the vitamin D receptor in tissues not normally involved in calcium homeostasis (such as mammary gland, pancreas and cells of the immune system) suggested additional roles for this hormone, and led to the identification of 1,25(OH)2D3 as a potent regulator of cell differentiation and proliferation. Studies from a number of laboratories have clearly demonstrated that 1,25(OH)2D3 inhibits growth of breast cancer cells in vitro, and causes regression of tumors growing in vivo (1–3), however, the underlying mechanism of the effect of vitamin D has yet to be clarified.
KeywordsBreast Cancer Cell Human Breast Cancer Cell Breast Cancer Cell Proliferation Breast Cancer Cell Growth Nuclear Matrix Protein
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