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

Int J Cancer. 2002 Jan 1;97(1):7-14. doi: 10.1002/ijc.1572.


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.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Blotting, Western
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Small Cell / pathology
  • Cell Communication
  • Collagen / chemistry
  • DNA Primers / chemistry
  • Doxycycline / pharmacology
  • Drug Combinations
  • ErbB Receptors / genetics*
  • Gene Expression
  • Humans
  • Immunoenzyme Techniques
  • Laminin / chemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Microscopy, Electron
  • Mutation*
  • Neoplasm Invasiveness
  • Proteoglycans / chemistry
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Tumor Cells, Cultured


  • Anti-Bacterial Agents
  • DNA Primers
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • RNA, Messenger
  • epidermal growth factor receptor VIII
  • matrigel
  • Collagen
  • ErbB Receptors
  • Doxycycline