Late SV40 factor:A key mediator of Notch signaling in human hepatocarcinogenesis

作     者：Ren-Hua Fan Jing Li Nan Wu Ping-Sheng Chen 

作者机构：Department of PathologySchool of MedicineSoutheast UniversityNanjing 210009Jiangsu ProvinceChina 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2011年第17卷第29期

页      面：3420-3430页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 071006[理学-神经生物学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：Supported by The National Natural Science Foundation of China No.30470780 

主　　题：Notch receptor Late SV40 factor Signal transduction Hepatocellular carcinoma 

摘      要：AIM:To investigate the relationship between late SV40 factor(LSF)and Notch signaling in the development and progress of hepatocellular carcinoma(HCC).METHODS:Liver cancer tissue specimens from 25 patients were analyzed for Notch-1 and LSF expression by *** correlation between expression and the biological effects of Notch-1 and LSF were analyzed using genetic and pharmacological strategies in HCC cell lines and human normal cell lines,including hepatic stellate cells(HSC)and human embryonic kidney epithelial cells(HEK).RESULTS:Immunohistochemistry showed that both Notch-1 and LSF were significantly upregulated in HCC samples(76%,19/25,P0.0001 and 84%,21/25,P0.0001,respectively)compared with non-cancer *** of Notch-1 by exogenous transfection of Notch1 intracellular domain increased LSF expression in HSC and HEK cells to levels similar to those seen in HepG2 ***,blocking Notch-1 activation with aγ-secretase inhibitor,DAPT,downregulated LSF expression in HepG2 ***,a biological behavior assay showed that forced overexpression of LSF promoted HepG2 cell proliferation and ***:LSF is a key mediator of the Notch signaling pathway,suggesting that it might be a novel therapeutic target for the treatment of HCC.