The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development.
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.
Pubmed ID: 10943841 RIS Download
Animals | Apoptosis | Cell Transformation, Neoplastic | Cells, Cultured | Fibroblasts | Humans | Keratinocytes | Mice | Mice, Inbred C57BL | Mice, Inbred CBA | Mice, Nude | Mice, Transgenic | Mitogen-Activated Protein Kinase 1 | Mitogen-Activated Protein Kinase 3 | Mitogen-Activated Protein Kinases | Papilloma | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-akt | Receptor, Epidermal Growth Factor | Signal Transduction | Skin Neoplasms | Son of Sevenless Proteins | ras Proteins