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
- Sibilia M
- Fleischmann A
- Behrens A
- Stingl L
- Carroll J
- Watt FM
- Schlessinger J
- Wagner EF
July 21, 2000
- Cell Transformation, Neoplastic
- Cells, Cultured
- Mice, Inbred C57BL
- Mice, Inbred CBA
- Mice, Nude
- Mice, Transgenic
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Mitogen-Activated Protein Kinases
- 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
- Adenocarcinoma of lung, response to tyrosine kinase inhibitor in is related to gene EGFR which is autosomal recessive according to the OMIM database.
- Fibromatosis, gingival is related to genes SOS1, GINGF, GF1, HGF, NS4 which are autosomal dominant according to the OMIM database.
- Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in is related to gene EGFR which is autosomal recessive according to the OMIM database.
- Nonsmall cell lung cancer, susceptibility to is related to gene EGFR which is autosomal recessive according to the OMIM database.
- Noonan syndrome 4 is related to genes SOS1, GINGF, GF1, HGF, NS4 which are autosomal dominant according to the OMIM database.