MAPK信号传导通路对人炎性乳腺癌细胞系侵袭能力的影响

Effects of MAPK on a human inflammatory breast carcinoma cell line

目的:本研究探讨上皮钙粘蛋白(E-cadherin)基因显性负调控质粒(pcDNA3.1(-)H-2kd-E-cadherin)导入SUM149细胞系后,对丝裂原活化蛋白激酶信号传导系统(mitogenactivatedproteinkinasecascade,MAPK)的相关信号通路及调控机制的改变情况。方法:应用蛋白印迹法,检测了人炎性乳腺癌细胞系SUM149、E-cadherin基因显性负调控突变体高表达的SUM149阳性克隆中MAPK激酶活性的变化。结果:与对照组(未转染及空质粒组)相比,转染后并稳定高表达小鼠H-2kd阳性克隆的细胞中,磷酸化的细胞外信号调节激酶(extracellularsignalregulatedkinase,p-ERK1/2,phospho-P44/42)明显降低;而磷酸化P38激酶无显著变化。结论:在异常高的E-cadherin功能性表达人炎性乳腺癌细胞系SUM149中,下调上皮钙粘着蛋白表达明显抑制其侵袭能力。其可能通过下调丝裂原活化蛋白激酶信号传导系统MAPK中的磷酸化细胞外信号调节激酶(phos-extracellularsignalregulatedkinase)phos-Erk1/2降低基质金属蛋白酶MMP-1、MMP-9等表达,从而明显抑制其侵袭能力。

Purpose： To invastigate the changes of the related signaling pathways and it＇s mechanism of reguation of mitogen activated protein kinase cascade（MAPK）by SUM149 cells induced plasmid of dominant-negative E-cadherin mutant H-2k^d-E-cadherin.Methods：Using western blot method.we examined the signal pathway of mitogen activated protein kinase（MAPK）between the domiant-negative mutant E-cadherin transfected SUM149 cells and controls.Results：Compared with the controls,the phosphorylated extracellular signal regulated kinase P44/42 expression of the SUM149 cells which expressed higher dominant-negative mutant E-cadherin was significantly down-regulated.Conclusions：In this cell line model,the down-regulation of P44/42 may involve the regulation of MMPs.