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Int J Cancer. 2002 Jan 1;97(1):7-14.

Epidermal growth factor receptor mutation type III transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype.

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Department of Radiation Biology, The Finsen Center, University Hospital Copenhagen, Copenhagen, Denmark.


In the present study we transfected the epidermal growth factor receptor (EGFR)-negative small cell lung cancer cell line, GLC3, with the type III EGFR mutation (EGFRvIII). The EGFRvIII protein could be detected by Western blot analysis as a 145-kDa protein, which by immunohistochemistry appeared to be localized at the cell surface. Ultrastructurally EGFRvIII was expressed mainly at the cell surface with clusters at cell-cell contacts. In the in vitro invasion assay, GLC3-EGFRvIII cells had a approximately 5-fold increased invasion compared with uninduced GLC3-EGFRvIII, GLC3-Tet-On and the parental cell line. GLC3-Tet-On appeared uniform in size with adherence junctions at cell-cell contacts. In uninduced GLC3-EGFRvIII cells adherence junctions were also present but less distinct. In doxycycline-pretreated GLC3-EGFRvIII cells, adherence junctions were absent. We conclude that the expression of EGFRvIII results in a more malignant phenotype. This effect appears to involve the disruption of adherence junctions.

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