Gab1在胃癌组织中表达分析及通过PI3K/AKT通路调控转移的机制研究

目的 探究Grb2相关结合蛋白1(Gab1)表达在胃癌中的临床意义和通过PI3K/AKT通路调控转移的机制.方法 收集2015年3月至2018年3月胃癌组织和癌旁组织标本各70份,通过免疫组织化学染色检测Gab1表达水平,并分析Gab1表达水平与患者一般资料和病理特点的相关性.将胃腺癌细胞AGS分为空白组、对照组、Ga...

Expression analysis of Gab1 in gastric cancer and the mechanism of regulating metastasis through PI3K/AKT pathway

Objective To explore the clinical significance of Grb2-associated binding protein 1(Gab1)expression in gastric cancer and the mechanism of regulating metastasis through PI3K/AKT pathway.Methods A total of 70 gastric cancer tissues and 70 adjacent tissues were collected from March 2015 to March 2018.The expression of Gab1 was detected by immunohistochemical staining.The correlation between Gab1 expression level and general information and pathology characteristics was analyzed.Gastric adenocarcinoma cell AGS was divided into blank group,control group,Gab1 group and Gab1+LY294002 group.Gab1 was overexpressed by transfection of the pCMV6-entry-Gab1 recombinant plasmid in the Gab1 group.The cells were transfected negative control plasmid in the control group.In the Gab1+LY294002 group,PI3K/AKT inhibitor LY294002(5μmol/L)was added in the medium in the Gab1+LY294002 group.Gab1 mRNA relative expression level was detected by qPCR,and Gab1,p-AKT and AKT protein levels were detected by Western blot.Cell viability,migration,and invasion were measured by CCK-8 method,cell scratch test,and Transwell test,respectively.Results Gab1 was scarcely expressed in adjacent tissues,but its expression level was increased in gastric cancer tissues.The number of cases of high expression level of Gab1 in patients with lymph node metastasis,distal metastasis,T3+T4 infiltration depth,stageⅢ-Ⅳwas more than that of of cases of high expression level of Gab1 patients without lymph node metastasis,distal metastasis,T1+T2 infiltration depth and stageⅠ-Ⅱpatients(P<0.05).The Gab1 mRNA relative expression level and protein expression in the Gab1 group and Gab1+LY294002 group were significantly higher than those in the blank group and the control group(P<0.05).LY294002 had no significant effect on the expression of Gab1 mRNA and protein.The cell viability,migration and invasion abilities in the Gab1 group were significantly higher than those in the blank group,the control group and the Gab1+LY294002 group(P<0.05).The level of AKT phosphorylation in the Gab1 group was significantly higher than that in the blank group,the control group and the Gab1+LY294002 group(P<0.05).Conclusion Gab1 is highly expressed in gastric cancer tissues,and high expression levels of Gab1 are associated with the malignant phenotype of gastric cancer.Up-regulation of Gab1 expression would promote the cell migration and invasion of gastric cancer cells by activating the PI3K/AKT pathway.