androgen receptor variants occur frequently in castration resistant prostate cancer metastases雄激素受体在阉割抗前列腺癌转移经常发生变异现象.pdfVIP

Androgen Receptor Variants Occur Frequently in Castration Resistant Prostate Cancer Metastases 1 1 2 1 2,3 Xiaotun Zhang , Colm Morrissey , Shihua Sun , Melanie Ketchandji , Peter S. Nelson , Lawrence D. 4 4 1,5 2,5 True , Funda Vakar-Lopez , Robert L. Vessella , Stephen R. Plymate * 1 Department of Urology, University of Washington, Seattle, Washington, United States of America, 2 Department of Medicine, University of Washington, Seattle, Washington, United States of America, 3 Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 4 Department of Pathology, University of Washington, Seattle, Washington, United States of America, 5 GRECC and Research Service, Department of Veterans Affairs Medical Center, Seattle, Washington, United States of America Abstract Background: Although androgens are depleted in castration resistant prostate cancer (CRPC), metastases still express nuclear androgen receptor (AR) and androgen regulated genes. We recently reported that C-terminal truncated constitutively active AR splice variants contribute to CRPC development. Since specific antibodies detecting all C-terminal truncated AR variants are not available, our aim was to develop an approach to assess the prevalence and function of AR variants in prostate cancer (PCa). Methodology/Principal Findings: Using 2 antibodies against different regions of AR protein (N- or C-terminus), we successfully showed the existence of AR variant in the LuCaP 86.2 xenogra