Differential expression of prohibitin is correlated with dual action of Vitamin D as a proliferative and antiproliferative hormone in breast epithelial cells

Our previous microarray analysis showed that N-methyl-N-nitrosourea (MNU) transformed MCF12F breast epithelial cells exhibited upregulation of several genes, including prohibitin, which was reversed by 1α-hydroxyvitamin D5 (1α(OH)D5) treatment. The in silico screening for putative transcription factor binding sites identified two VDR/RXR binding sites in the 1 kb promoter region of prohibitin. Other binding sites for EGR and GR which are also Vitamin D target genes were identified in this region, indicating that prohibitin is a potential target gene for Vitamin D. The combination of multiple binding sites also provides a basis for a possible dual regulation of prohibitin by Vitamin D. Prohibitin upregulation by 1α(OH)D5 treatment at both transcription and translation level was observed in Vitamin D sensitive BT474 breast cancer cells, in which 1α(OH)D5 significantly inhibited cell proliferation in normal culture condition. On the other hand, prohibitin down-regulation accompanied with Vitamin D mediated maintenance of proliferation of breast epithelial cells was observed under stressed condition. These results demonstrated that Vitamin D mediated antiproliferative activity in unstressed condition and growth maintaining activity under stressed condition involve differential expression of prohibitin.