functional significance of vitamin d receptor foki polymorphism in human breast cancer cells维生素d受体的功能意义foki多态性在人类乳腺癌细胞.pdfVIP

Functional Significance of Vitamin D Receptor FokI Polymorphism in Human Breast Cancer Cells 1,2 1 1,2 1,2 Fatouma Alimirah , Xinjian Peng , Genoveva Murillo , Rajendra G. Mehta * 1 Division of Cancer Biology, IIT Research Institute, Illinois Institute of Technology, Chicago, Illinois, United States of America, 2 Department of Biological Chemical and Physical Sciences, Illinois Institute of Technology, Chicago, Illinois, United States of America Abstract Background: The FokI vitamin D receptor (VDR) polymorphism results in different translation initiation sites on VDR. In the VDRff variant, initiation of translation occurs at the first ATG site, giving rise to a full length VDR protein of 427 amino acids. Conversely, in the VDRFF variant, translation begins at the second ATG site, resulting in a truncated protein with three less amino acids. Epidemiological studies have paradoxically implicated this polymorphism with increased breast cancer risk. 1a,25 (OH) D , the active metabolite of vitamin D, is known to inhibit cell proliferation, induce apoptosis and potentiate 2 3 differentiation in human breast cancer cells. It is well documented that 1a,25 (OH)2D3 downregulates estrogen receptor a expression and inhibits estrogen mediated signaling in these cells. The functional significance of the VDR FokI polymorphism in vitamin D action is undefined. Methods/Findings: To elucidate the functional role of FokI polymorphism in breast cancer, MCF-7-Vector, MCF-7-VDRff and MCF-7-VDRFF stable cell lines were established from parental MCF-7 cells as single-cell clones. In response to 1a,25 (OH) D