PTEN inhibited the invasion of glioma cells with a common mutant epidermal growth factor receptor expression by dephosphorylating FAK / 中国癌症杂志

ABSTRACT

Background and purpose:PTEN mutation has been found in 20%-40% of malignant gliomas.The common mutant epidermal growth factor receptor(EGFR vⅢ)was reported to coexpress in PTEN-deficient EGFR-expressing tumor.PTEN has been shown to interact directly with FAK and reduce its tyrosine phosphorylation levels to inhibit cell invasion.The invasion of glioma cells with EGFRvⅢ expression and PTEN deficiency is increased.This study was to observe whether PTEN inhibits glioma cell invasion even in the presence of strong pro-invasive signals provided by constitutive EGFR activity.Methods:U87?EGFR cells were transfected with pcDNA3.1 constructs encoding PTEN and the cells invasion levels were detected by transwell invasion assay.The expression of FAK was detected by immunoblotting.FAK expression vector was transfected into U87?EGFR-wtPTEN cells and the change of cells invasion was documented.Results:PTEN and PTEN(G129E)could inhibit cell invasion induced by EGFRvⅢ.PTEN and PTEN(G129E)could decrease the FAK phosphorylation at Tyr397.Over expression of FAK in U87?EGFR-PTEN abrogated PTEN-induced down-regulation of the phosphorylation status of FAK and rescued cell invasion.Conclusions:PTEN could inhibit cell invasion induced by EGFRvⅢ by dephosphorylating FAK.