Author/Authors :
Maria Sibilia، نويسنده , , Alexander Fleischmann، نويسنده , , Axel Behrens، نويسنده , , Laura Stingl، نويسنده , , Joseph Carroll، نويسنده , , Fiona M. Watt، نويسنده , , Joseph Schlessinger and Kam Y. J.، نويسنده , , Erwin F. Wagner، نويسنده ,
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 ras V12, however, tumorigenicity is restored by expression of the anti-apoptotic bcl-2 gene. The K5-SOS-F papillomas and primary keratinocytes from 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.
