Epidermal growth factor receptor expression in neurofibromatosis type 1-related tumors and NF1 animal models

J Clin Invest. 2000 May;105(9):1233-41. doi: 10.1172/JCI7610.


We have found that EGF-R expression is associated with the development of the Schwann cell-derived tumors characteristic of neurofibromatosis type 1 (NF1) and in animal models of this disease. This is surprising, because Schwann cells normally lack EGF-R and respond to ligands other than EGF. Nevertheless, immunoblotting, Northern analysis, and immunohistochemistry revealed that each of 3 malignant peripheral nerve sheath tumor (MPNST) cell lines from NF1 patients expressed the EGF-R, as did 7 of 7 other primary MPNSTs, a non-NF1 MPNST cell line, and the S100(+) cells from each of 9 benign neurofibromas. Furthermore, transformed derivatives of Schwann cells from NF1(-/-) mouse embryos also expressed the EGF-R. All of the cells or cell lines expressing EGF-R responded to EGF by activation of downstream signaling pathways. Thus, EGF-R expression may play an important role in NF1 tumorigenesis and Schwann cell transformation. Consistent with this hypothesis, growth of NF1 MPNST lines and the transformed NF1(-/-) mouse embryo Schwann cells was greatly stimulated by EGF in vitro and could be blocked by agents that antagonize EGF-R function.

Publication types

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

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / metabolism*
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Neurilemmoma
  • Neurofibromatosis 1 / metabolism*
  • Neurofibromin 1
  • Proteins / genetics*
  • Rats
  • Tumor Cells, Cultured


  • Neurofibromin 1
  • Proteins
  • Epidermal Growth Factor
  • ErbB Receptors