anti-cancer drugs elicit re-expression of udp-glucuronosyltransferases in melanoma cellsudp-glucuronosyltransferases在黑色素瘤细胞的抗癌药物引起的表达.pdfVIP

Anti-Cancer Drugs Elicit Re-Expression of UDP- Glucuronosyltransferases in Melanoma Cells 1,2 3 3 3 Ryan W. Dellinger *, Harry H. Matundan , Amelia S. Ahmed , Priscilla H. Duong , Frank L. Meyskens Jr.1,2,3,4 1 Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California, United States of America, 2 Department of Medicine, University of California Irvine, Irvine, California, United States of America, 3 Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America, 4 Department of Public Health, University of California Irvine, Irvine, California, United States of America Abstract The UDP-glucuronosyltransferase (UGT) family of enzymes plays a vital role in the detoxification of carcinogens as well as clearance of anti-cancer drugs. In humans, 19 UGT family members have been identified and are expressed in a tissue specific manner throughout the body. However, the UGTs have not been previously characterized in melanocytes or melanoma. In the present study, UGT2B7, UGT2B10, and UGT2B15 were identified as being normally expressed in human melanocytes. The same three UGT family members were also expressed in the primary melanoma cell line WM115. No UGT expression was detected in another primary melanoma cell line, WM3211, or in any metastatic melanoma cell line examined. These results suggest that UGT expression is lost during melanoma progression. Treatment of WM3211 or metastatic melanoma cell lines with anti-cancer agents (including vemurafenib) induced expression of UGT2B7, UGT2B10 and UGT2B15 demonstrating that melanoma cells retain the ability to re-express these same three UGTs. The corresponding increase in