The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development

Cell. 2000 Jul 21;102(2):211-20. doi: 10.1016/s0092-8674(00)00026-x.

Abstract

The EGF receptor (EGFR) is required for skin development and is implicated in epithelial tumor formation. Transgenic mice expressing a dominant form of Son of Sevenless (SOS-F) in basal keratinocytes develop skin papillomas with 100% penetrance. However, tumor formation is inhibited in a hypomorphic (wa2) and null EGFR background. Similarly, EGFR-deficient fibroblasts are resistant to transformation by SOS-F and rasV12, however, tumorigenicity is restored by expression of the anti-apoptotic bcl-2 gene. The K5-SOS-F papillomas and primary keratinocytesfrom wa2 mice display increased apoptosis, reduced Akt phosphorylation and grafting experiments imply a cell-autonomous requirement for EGFR in keratinocytes. Therefore, EGFR functions as a survival factor in oncogenic transformation and provides a valuable target for therapeutic intervention in a broader range of tumors than anticipated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Fibroblasts / cytology
  • Humans
  • Keratinocytes / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Nude
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Papilloma / metabolism*
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction*
  • Skin Neoplasms / metabolism*
  • Son of Sevenless Proteins / genetics
  • Son of Sevenless Proteins / metabolism*
  • ras Proteins / metabolism

Substances

  • Proto-Oncogene Proteins
  • Son of Sevenless Proteins
  • ErbB Receptors
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • ras Proteins