| Literature DB >> 10943841 |
M Sibilia1, A Fleischmann, A Behrens, L Stingl, J Carroll, F M Watt, J Schlessinger, E F Wagner.
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.Entities:
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Year: 2000 PMID： 10943841 DOI： 10.1016/s0092-8674(00)00026-x
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582