Deng Zheng-Hao, Wen Ji-Fang, Li Jing-He, Xiao De-Sheng, Zhou Jian-Hua
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan Province, China.
World J Gastroenterol. 2008 Mar 7;14(9):1437-43. doi: 10.3748/wjg.14.1437.
To investigate the role of Ras association domain family protein 1 isoform A (RASSF1A) in gastric tumorigenesis.
Through over-expression of RASSF1A gene in the SGC7901 cell line which was induced by a lipofectamine-mediated gene transfer approach. Activator protein-1 (AP-1) DNA binding activity was measured by electrophoretic mobility shift assay (EMSA).
Compared with the control clones, cells over-expressing RASSF1A exhibited significant inhibition of cell growth with G1 cell cycle arrest in vitro and in vivo. The over-expression of RASSF1A significantly inhibited AP-1 activity in SGC7901 cells (0.981+/-0.011 vs 0.354+/-0.053, P<0.001). In addition, both Western blot analysis and immunocytochemistry demonstrated that RASSF1A down-regulated the expression of c-Fos (0.975+/-0.02 vs 0.095+/-0.024, P<0.001) but not c-Jun.
Over-expression of RASSF1A inhibits the growth of SGC7901 cells by negatively regulating the AP-1 activity, the latter in turn negatively signals cell proliferation.
研究Ras关联结构域家族蛋白1亚型A（RASSF1A）在胃癌发生中的作用。
通过脂质体介导的基因转染方法，在SGC7901细胞系中过表达RASSF1A基因。采用电泳迁移率变动分析（EMSA）检测激活蛋白-1（AP-1）的DNA结合活性。
与对照克隆相比，过表达RASSF1A的细胞在体外和体内均表现出细胞生长的显著抑制，细胞周期停滞于G1期。RASSF1A的过表达显著抑制了SGC7901细胞中的AP-1活性（0.981±0.011对0.354±0.053，P<0.001）。此外，蛋白质免疫印迹分析和免疫细胞化学均表明，RASSF1A下调了c-Fos的表达（0.975±0.02对0.095±0.024，P<0.001），但未下调c-Jun的表达。
RASSF1A的过表达通过负调控AP-1活性抑制SGC7901细胞的生长，而AP-1活性反过来又对细胞增殖产生负信号。
