Protection Against Cellular Stress by 25-Hydroxyvitamin D3 in Breast Epithelial Cells

25-Hydroxyvitamin D-3 (25(OH)D-3) is a prohormone and a major vitamin D metabolite. The discovery of (25(OH)D-3) 1 alpha-hydroxylase in many vitamin D target organs has yielded an increased interest in defining the role(s) of 25(OH)D-3 in these tissues. The etiology of cancer appears to be complex and multi-factorial. Cellular stress (e.g., DNA damage, hypoxia, oncogene activation) has been identified as one of the key factors responsible for initiating the carcinogenesis process. In this study, we investigated whether 25(OH)D-3 protects breast epithelial cells from cellular stress using an established breast epithelial cell line MCF12F. To better elucidate the role of 25(OH)D-3 in the stress response, we used multiple in vitro stress models including serum starvation, hypoxia, oxidative stress, and apoptosis induction. Under all these stress conditions, 25(OH)D-3 (250 nmol/L) treatment significantly protected cells against cell death. Low-serum stress induced p53 expression accompanied with downregulation of PCNA, the presence of 25(OH)D-3 consistently inhibited the alteration of p53 and PCNA, suggesting that these molecules were involved in the stress process and may be potential target genes of 25(OH)D-3. miRNA microarray analysis demonstrated that stress induced by serum starvation caused significant alteration in the expression of multiple miRNAs including miR182, but the presence of 25(OH)D-3 effectively reversed this alteration. These data suggest that there is a significant protective role for 25(OH)D-3 against cellular stress in the breast epithelial cells and these effects may be mediated by altered miRNA expression. J. Cell. Biochem. 110: 1324-1333, 2010. (C) 2010 Wiley-Liss, Inc.