The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development.
Journal:
Cell 2000 JulAuthors:
Sibilia M, Fleischmann A, Behrens A, Stingl L, Carroll J, Watt FM, Schlessinger J, Wagner EF
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-
...[more]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.[less]
Mesh Headings:
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