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 o f Son of Sevenless (SOS-F) in basal keratinocytes develop skin papillomas w ith 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 papi llomas and primary keratinocytes from wa2 mice display increased apoptosis, reduced Akt phosphorylation and grafting experiments imply a cell-autonomo us requirement for EGFR in keratinocytes. Therefore, EGFR functions as a su rvival factor in oncogenic transformation and provides a valuable target fo r therapeutic intervention in a broader range of tumors than anticipated.