You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2010229 HOW DOES ETS FAMILY CONTRIBUTE TO PROSTATE CANCER PROGRESSION? Takeo Kosaka, Akira Miyajima, Shuji Mikami, Eiji Kikuchi, Suguru Shirotake, Takahiro Maeda, and Mototsugu Oya Takeo KosakaTakeo Kosaka More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , Shuji MikamiShuji Mikami More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Suguru ShirotakeSuguru Shirotake More articles by this author , Takahiro MaedaTakahiro Maeda More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.287AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recurrent gene fusions between TMPRSS2 and the ETS transcription factors have been identified in prostate cancer (PCa) development. However, the function of fusion products has not been well characterized. We previously showed long-term androgen ablation induced Ets-1 up-regulation in prostate cancer (Kosaka T, Prostate 2009). In this study, we examined the expression and the function of Ets-1, and determined its prognostic significance and correlation with hormone-independency. METHODS Total 139 human PCa specimens: 119 specimens (group AD) from patients who underwent radical prostatectomy for localized PCa and 20 specimens (group HR) from patients who died of hormone-refractory prostate cancer (HRPC) were enrolled in this study. Immunohistochemistry (IHC) was used to investigate Ets-1 and CD34:MVD. The median follow up was 70.5 months. Progression free survival was calculated by the Kaplan-Meier method. Multivariate analysis was performed using Cox regression model. Three human PCa cell lines LNCaP, C4-2, and C4-2AT6 (Established at our laboratory under androgen-ablated condition medium, Prostate 2009) were analyzed in vitro and in vivo. Ets-1 expression was transiently down-regulated using siRNA directed against Ets-1 (si-Ets-1). RESULTS The expression of Ets-1 in the nucleus and MVD in group HR were significantly higher than group AD (p<0.001). There was s significant positive correlation between Ets-1 and MVD (Spearman′s correlation, r=0.752, p<0.001). There were statistically significant correlation between Ets-1 expression and MVD (p<0.001), and extracapsular extension of cancer (ECE) (p<0.001). During a median 70.5 months follow-up period, PSA failure was confirmed in 30 patients. There were significant differences in PSA failure-free survival (log-rank test, p<0.001), ECE (p<0.001) with regard to Ets-1 expression, MVD, ECE, and LVI. The 5-year PSA failure-free survival was 43.0% for patients with higher Ets-1 expression compared to 88.8% for patients with lower Ets-1 expression. Multivariate Cox regression analysis indicated that higher Snail expression (p=0.002) and LVI (p=0.008) were independent prognostic factors. C4-2AT6 expressed Ets-1 in the nucleus more strongly than C4-2 and LNCaP cells in vitro and in vivo, accompanied by higher VEGF production. Knockdown of Ets-1 by si-Ets-1 resulted in a matched reduction in VEGF production in C4-2AT6 and C4-2. CONCLUSIONS These results indicated that increased expression of Ets-1 in the nucleus, which found to be prognostic indicator, were associated with angiogenesis and hormone-independency. Tokyo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e89-e90 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takeo Kosaka More articles by this author Akira Miyajima More articles by this author Shuji Mikami More articles by this author Eiji Kikuchi More articles by this author Suguru Shirotake More articles by this author Takahiro Maeda More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...