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Phosphorylated p70S6K in urothelial carcinoma of the tumor recurrence noninvasive low-grade bladder: correlation with

Phosphorylated p70S6K in urothelial carcinoma of the tumor recurrence noninvasive low-grade bladder: correlation with

作     者:Soon-Ja Kim Jung Hoon Kim Hui Seok Jung Tae-Jin Lee Kyung Mee Lee In Ho Chang 

作者机构:Department of Convergence Medicine and Pharmaceutical Biosciences Chung-Ang University Graduate School Seoul Department of Urology Department of Pathology Chung-Ang University College of Medicine Seoul Korea. 

出 版 物:《Asian Journal of Andrology》 (亚洲男性学杂志(英文版))

年 卷 期:2014年第16卷第4期

页      面:611-617页

核心收录:

学科分类:090603[农学-临床兽医学] 0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 09[农学] 0906[农学-兽医学] 

基  金:supported by the Department of Convergence Medicine and Pharmaceutical Biosciences Research Scholarship Grants 

主  题:bladder cancer p7OS6K 

摘      要:We investigated whether inhibiting phosphorylated p70S6K (p-p70S6K) suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma (LG-URCa) in vitro and whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray (TMA) for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group (P 〈 0.05; hazard ratio (HR), 2.415) and the high p-p70S6K staining group (P 〈 0.05; HR, 2.249) were independent factors for predicting recurrence. Rapamycin inhibited RT4 and 253J cell proliferation in a dose-dependent manner (r = -0.850, P 〈 0.001 in RT4 cells; r = -0.835, P 〈 0.001 in 253J cells). RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively (P 〈 0.05). Transfection of p70S6K siRNA resulted in inhibitory effects on cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder.

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