Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis

Cancer Cell. 2005 Jan;7(1):65-75. doi: 10.1016/j.ccr.2004.10.016.

Abstract

Benign neurofibromas and malignant peripheral nerve sheath tumors are serious complications of neurofibromatosis type 1. The epidermal growth factor receptor is not expressed by normal Schwann cells, yet is overexpressed in subpopulations of Nf1 mutant Schwann cells. We evaluated the role of EGFR in Schwann cell tumorigenesis. Expression of EGFR in transgenic mouse Schwann cells elicited features of neurofibromas: Schwann cell hyperplasia, excess collagen, mast cell accumulation, and progressive dissociation of non-myelin-forming Schwann cells from axons. Mating EGFR transgenic mice to Nf1 hemizygotes did not enhance this phenotype. Genetic reduction of EGFR in Nf1(+/-);p53(+/-) mice that develop sarcomas significantly improved survival. Thus, gain- and loss-of-function experiments support the relevance of EGFR to peripheral nerve tumor formation.

Publication types

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

MeSH terms

  • 2',3'-Cyclic-Nucleotide Phosphodiesterases / genetics
  • 2',3'-Cyclic-Nucleotide Phosphodiesterases / metabolism
  • Animals
  • Cells, Cultured
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Fibrosis
  • Humans
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasms, Nerve Tissue / genetics
  • Neoplasms, Nerve Tissue / metabolism
  • Neoplasms, Nerve Tissue / pathology
  • Neurofibroma / genetics
  • Neurofibroma / metabolism*
  • Neurofibroma / pathology
  • Neurofibromatosis 1 / genetics
  • Neurofibromatosis 1 / metabolism*
  • Neurofibromatosis 1 / pathology*
  • Neurofibromin 1 / genetics
  • Neurofibromin 1 / metabolism
  • Peripheral Nerves / metabolism*
  • Peripheral Nerves / pathology*
  • Peripheral Nerves / ultrastructure
  • Schwann Cells / cytology
  • Schwann Cells / physiology*
  • Signal Transduction / physiology
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Neurofibromin 1
  • Tumor Suppressor Protein p53
  • ErbB Receptors
  • 2',3'-Cyclic-Nucleotide Phosphodiesterases