role of tmprss2-erg gene fusion in negative regulation of psma expressiontmprss2-erg基因融合在负调节psma表达式.pdfVIP

Role of TMPRSS2-ERG Gene Fusion in Negative Regulation of PSMA Expression 1 2 3 4 4 1,2 Lihong Yin , Pravin Rao , Paul Elson , Jianghua Wang , Michael Ittmann , Warren D. W. Heston * 1 Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio, United States of America, 2 Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, United States of America, 3 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States of America, 4 Department of Pathology and Immunology, Baylor College of Medicine, and the Michael E. DeBakey Veterans Affairs Medical Center (VAMC), Houston, Texas, United States of America Abstract Prostate specific membrane antigen (PSMA) is overexpressed in prostatic adenocarcinoma (CaP), and its expression is negatively regulated by androgen stimulation. However, it is still unclear which factors are involved in this downregulation. TMPRSS2-ERG fusion is the most common known gene rearrangement in prostate carcinoma. Androgen stimulation can increase expression of the TMPRSS2-ERG fusion in fusion positive prostate cancer cells. The purpose of this investigation is to determine whether PSMA expression can be regulated by the TMPRSS2-ERG gene fusion. We employed two PSMA positive cell lines: VCaP cells, which harbor TMPRSS2-ERG fusion, and LNCaP cells, which lack the fusion. After 24 hours of androgen treatment, TMPRSS2-ERG mRNA level was increased in VCaP cells. PSMA mRNA level was dramatically decreased in VCaP cells, while it only has moderate change in LNCaP cells. Treatment with the androgen antagonist flutamide partially restored PSMA expression in androgen-treated VCaP cells. Knocking down ERG by siRNA i