Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts

Cell. 1989 Jul 28;58(2):287-92. doi: 10.1016/0092-8674(89)90843-x.


The protein product of the rodent neu oncogene, p185neu, is a tyrosine kinase with structural similarity to the epidermal growth factor receptor (EGFR). Transfection and subsequent overexpression of the human p185c-erbB-2 protein transforms NIH 3T3 cells in vitro. However, NIH 3T3 cells are not transformed by overexpressed rodent p185c-neu. NIH 3T3 transfectants overexpressing EGF receptors are not transformed unless incompletely transformed. Several groups have recently demonstrated EGF-induced, EGFR-mediated phosphorylation of p185c-neu. During efforts to characterize the interaction of p185c-neu with EGFR further, we created cell lines that simultaneously overexpress both p185c-neu and EGFR and observed that these cells become transformed. These observations demonstrate that two distinct, overexpressed tyrosine kinases can act synergistically to transform NIH 3T3 cells, thus identifying a novel mechanism that can lead to transformation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Fibroblasts / ultrastructure
  • Gene Expression Regulation
  • Mice
  • Mice, Nude
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptor, ErbB-2
  • Transfection


  • Proto-Oncogene Proteins
  • ErbB Receptors
  • Receptor, ErbB-2