Gab2通过调节EMT促进胃癌的侵袭转移

陈美玲; 姜迎宵; 王淑晓; 孙秀宁; 张小茜; 郑书贤; 张宝刚; 史立宏

doi:10.3971/j.issn.1000-8578.2018.17.0881

Gab2通过调节EMT促进胃癌的侵袭转移

Gab2 Promotes Invasion and Metastasis of Gastric Cancer via Regulating EMT

摘要

摘要:
目的探讨Gab2在胃癌组织中的表达情况及其对胃癌细胞侵袭转移能力的影响与机制。
方法采用免疫组织化学SP法检测胃癌组织中Gab2、E-cadherin、N-cadherin及MMP-9的表达并分析其与淋巴结转移的关系。应用小RNA干扰技术，转染SGC7901细胞株，RT-PCR法检测瞬时转染后Gab2基因表达情况，体外侵袭实验检测细胞转染后侵袭能力的变化，Western blot法检测各蛋白的表达。
结果胃癌组织中Gab2的表达水平与淋巴结转移显著相关（P=0.002），与E-cadherin的表达负相关（r=-0.693, P=0.000），而与N-cadherin和MMP-9的表达水平正相关（r=0.407, P=0.021; r=0.335, P=0.017）。小RNA干扰技术降低Gab2蛋白的表达后SGC7901细胞侵袭转移能力降低，同时E-cadherin表达增多，N-cadherin和MMP-9蛋白表达降低。
结论 Gab2可能通过调节EMT在胃癌侵袭转移中发挥重要作用。

Abstract:
Objective To investigate the expression of Grb2 binding protein-2(Gab2) in gastric cancers and its significance and mechanism in the invasiveness and metastasis of gastric cancer.
Methods Immunohistochemical method was used to detect the expression of Gab2, E-cadherin, N-cadherin and MMP-9 in gastric cancer tissues. The relationship between Gab2 expression and lymphatic metastasis was analysed. SiRNA plasmid targeting Gab2 and empty vector plasmid were transfected into SGC7901 cells and named siGab2/SGC7901 and NC/SGC7901 cells respectively. RT-PCR method was applied to analyze mRNA expression of Gab2 in siGab2/SGC7901 and NC/SGC7901 cells. In vitro matrigel invasion assay was used to detect the invasiveness of siGab2/SGC7901 and SGC7901 cells. Western blot was applied to analyze protein expression.
Results Gab2 expression in gastric cancer tissues was related with lymphatic metastasis significantly(P=0.002), E-cadherin expression level negatively (r=-0.693, P=0.000), and N-cadherin and MMP-9 levels positively (r=0.407, P=0.021; r=0.335, P=0.017). After microRNA interference, the mRNA and protein expressions of Gab2 in siGab2/SGC7901 cells were decreased obviously, moreover, the quantity of gastric cancer cells which invaded and penetrated matrigel membrane was decreased. Western blot showed that the expressions of N-cadherin and MMP-9 were decreased and E-cadherin expression was increased in siGab2/SGC7901 cells.
Conclusion Gab2 plays a key role in the invasiveness and metastasis of gastric cancer by regulating EMT.

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