肝细胞癌TGF-β受体表达的改变——一种组成性活性TGF-βI型受体突变体的效应

作     者：Musch A. Rabe C. Paik M.-D. 张诗峰 

作者机构：Sigmund-Freud-Strasse 25 DE-53105 Bonn Germany 

出 版 物：《世界核心医学期刊文摘（胃肠病学分册）》 (Core Journals in Gastroenterology)

年 卷 期：2005年第1卷第9期

页      面：14-15页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：TGF-β受体 肝细胞癌 I型受体 突变体 种组 侵袭力 瞬时转染 整联蛋白 稳定转染 抑制作用 

摘      要：Background/Aims: Hepatocellular carcinomas (HCC) often show resistance to the effects of transforming growth factor-β(TGF-β). This study focuses on molecular mechanisms of this resistance to explore ways to overcome it. Methods: Transcription and protein expression of TGF-βtype I and type II receptors (TGF-βRI/RII) were analyzed in clinical HCCs and the human hepatoma cell lines HuH-7 and HepG2. HuH-7 cells were transiently and stably transfected with a constitutively active TGF-βRI mutant (CATGF-βRI). Resulting growth kinetics, integrin expression, invasiveness, TGF-β-mediated activation of human plasminogen activator inhibitor type-1 (PAI-1) promoter and Smad expression were determined. Results: In clinical HCCs, there was less TGF-βRII (6/10 cases) and more TGF-βRI (8/10 cases) protein expression detectable in tumor compared to adjacent liver tissue. In HuH-7 cells, TGF-βRII expression was likewise decreased. Cells transiently transfected with CA TGF-βRI exhibited strong TGF-β-related PAI-1 promoter activation. Stably transfected cells showed an attenuated response of the PAI-1 promoter, but increased Smad7 expression. Proliferation of stable clones was decreased. There was no change in integrin expression or invasiveness. Conclusions: Decreased TGF-βRII protein expression might cause TGF-βresistance in a subset of clinical HCCs. Stable transfection with CA TGF-βRI reverses this in HuH-7 cells without increasing invasiveness.