胃癌细胞中SMAD-4与TGF-β通过抑制RAS/ERK途径促进PTEN表达(英文)  

SMAD-4 Cooperates with TGF-β to Enhance PTEN Expression Upon The Inhibition of RAS/ERK Pathway in Gastric Carcinoma Cells

作　　者：MATLOOB Ammar 潘丽娜[2] 潘虹[1] 陆军[1] 黄百渠[1] 

机构地区：[1]东北师范大学遗传与细胞研究所,长春130024 [2]天津师范大学生命科学学院,天津300387

出　　处：《生物化学与生物物理进展》2011年第6期543-550,共8页Progress In Biochemistry and Biophysics

基　　金：supported by grants from The National Natural Science Foundation of China(30971613,30671184)~~

摘　　要：SMAD-4在肿瘤抑制方面有重要作用,但它在肿瘤发生中的作用及其与细胞周期进程中的一种关键调控因子——PTEN(phosphatase and tensin homolog deleted on chromosome 10)的关系仍存在争议.分别在人胚肾细胞(293T)及人胃癌细胞(MGC-803)中研究SMAD-4及TGF-β信号通路对PTEN基因表达的影响.结果发现,在293T细胞中,SMAD-4与TGF-β促进PTEN表达,而MGC-803细胞中,SMAD-4与TGF-β抑制PTEN转录.进一步研究发现,胃癌细胞中,SMAD-4与转化生长因子β(TGF-β)对PTEN的抑制可被PD98059(MEK抑制剂)解除.此外,SMAD-4的核转移也明显促进PTEN表达,并且PD98059存在下,SMAD-4与TGF-β协同刺激可促进胃癌细胞凋亡.综上,实验发现,SMAD-4作为一种co-Smad蛋白,通过TGF-β信号途径影响PTEN表达.SMAD-4 plays an important role in tumor suppression though controversies still exist regarding its behavior in carcinogenesis and its relationship with the phosphatase and tensin homolog deleted on chromosome 10 （PTEN）, which is regarded as a key controller of cell cycle progression and cell growth. The role of SMAD-4 on PTEN expression was investigated through TGF-β signaling in 293T cells and in malignant gastric carcinoma MGC-803 cells. Results showed that SMAD-4 and TGF-β enhanced the expression of PTEN in 293T cells, while they suppressed PTEN expression in MGC-803 cells. However, this suppression was relieved upon the inhibition of RAS/ERK pathway. Moreover, the maximum expression of PTEN was achieved by the cooperation of SMAD-4 with TGF-β when SMAD-4 was translocated into the nucleus. Enhancement of early apoptosis of about three folds was achieved with this cooperation, compared with the action of TGF-β alone in MGC-803 cells. These findings shed light on the role of SMAD-4 as a co-Smad protein in TGF-β protein-signaling and in PTEN regulation.

关 键 词：SMAD-4 转化生长因子β1(TGF-β1) PTEN RAS/ERK 

分 类 号：Q2[生物学—细胞生物学] Q3