Mig-6通过负向调控EGFR通路抑制肺癌细胞增殖

摘要

Objective:To observe the expression of Mig-6 in non small cell lung cancer( NSCLC)and its rela-tionship with EGFR,and study the proliferation ability and EGFR pathway change in NSCLC cell line . Methods:Immunohistochemistry ,Western blot and real time PCR were used to detect the expression of Mig-6 and EGFR in NSCLC. In lung cancer cell we used Mig-6 plaimid to up-regulate Mig-6,siMig-6 method to down regulate Mig-6,the CCK-8 assy was used to detect the proliferation of both two cell lines,Western blot to detect the expres-sion of p-EGFR,p-EGFR and p-AKT in transfectioned A549 and BE1 cell line. Results:The expression of Mig-6 was down-regulated in NSCLC,it was negatively correlated with the expression of EGFR(P=0. 003). Up-reg-ulation of Mig-6 can inhibit the proliferation of A549 cell and the expression of p-EGFR,p-EGFR and p-AKT. Down-regulation of Mig-6 in BE1 by siRNA can prompt the proliferation ablity,and the expression of p-EGFR,p-EGFR and p-AKT were also increased. Conclusion:Mig-6 expression in lung cancer was negatively correlated with EGFR. In lung cancer cell lines Mig-6 can inhibit cell proliferation possibly through inhibition of EGFR down-stream pathways.%目的：观察Mig-6在非小细胞肺癌组织中的表达及其与EGFR表达的关系。在肺癌细胞系中探讨上、下调Mig-6表达后细胞增殖能力及 EGFR通路的变化。方法：用免疫组化，蛋白免疫印迹及实时定量PCR的方法检测肺癌及癌旁组织中Mig-6及EGFR的表达。在肺癌细胞系中通过使用Mig-6质粒和小干扰RNA分别上调和下调Mig-6，CCK-8法检测两株细胞系增殖能力，蛋白免疫印迹检测细胞中p-EG-FR、p-EGFR及p-AKT表达水平。结果：Mig-6在非小细胞肺癌组织中低表达（51.6%），并与EGFR表达呈负相关（ P=0.003）。在肺癌细胞系中，上调Mig-6表达可以抑制细胞增殖并抑制EGFR、ERK及AKT的磷酸化，下调Mig-6表达则能促进细胞增殖并促进EGFR、ERK及AKT的磷酸化。结论：Mig-6表达在肺癌中与EGFR呈负相关，在肺癌细胞系中Mig-6通过负向调控EGFR下游通路而抑制细胞增殖。