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 1alpha-hydroxyvitamin D(5) (1alpha(OH)D(5)) treatment. The in silico screening for putative transcription factor binding sites identified two VDR/RXR binding sites in the 1kb 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 1alpha(OH)D(5) treatment at both transcription and translation level was observed in Vitamin D sensitive BT474 breast cancer cells, in which 1alpha(OH)D(5) 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.
Peng
Xinjian
X
IIT Research Institute, 10 West 35th Street, Chicago, IL 60616, USA.
Mehta
Rajendra G
RG
D001483:Base Sequence; D001940:Breast / Q000187:drug effects* / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D014807:Vitamin D / Q000494:pharmacology*
D004100:Dihydroxycholecalciferols; D006728:Hormones; D034741:RNA, Small Interfering; D014807:Vitamin D; D001973:Bromodeoxyuridine