Aurora B

Already in the eighties it was shown that the active form of vitamin D 3 , 1,25-dihydroxyvi-tamin D 3 [1,25(OH) 2 D 3 ], can inhibit the proliferation of melanoma cells 1 and stimulate the differentiation of myeloid leukemia cells. 2 The almost universal presence of the vitamin D receptor (VDR) and the presence of 1α-hydroxylase (CyP27B1) activity in non-classical tissues together with the antiproliferative and prodifferentiating effects suggests a para-crine role for 1,25(OH) 2 D 3. 1,25(OH) 2 D 3 directly regulates the expression of a whole set of genes through binding to the VDR which het-erodimerizes to the retinoid X receptor (RXR), and 1,25(OH) 2 D 3-VDR/RXR complexes bind to vitamin D response elements in the promoter region of target genes. in most cancer cell types that express a functional VDR, exposure to 1,25(OH) 2 D 3 results in the accumulation of cells in the G 0 /G 1 phase of the cell cycle. This effect is not due to one single gene or a single pathway but depend on a multiple pathways among which epidermal growth factor, insulin like growth factor, transforming growth factor, prostaglandins and Wnt-β-catenin signaling cascades. 3 in VDR −/− mice there is no apparent increase in spontaneous cancer but these mice have an increased rate of proliferation of colonic, prostate and breast cells. 4 if VDR −/− mice are challenged with carcinogenic agents the incidence of skin tumors increase or more pre-neoplastic lesions in the mammary glands are present. Mouse mammary tumor virus (MMTV)-neu mice on VDR heterozygous background also show accelerated mammary tumorigenesis compared with MMTV-neu mice on VDR wild type background.