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The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development

被引：260
作者：
Sibilia, M
Fleischmann, A
Behrens, A
Stingl, L
Carroll, J
Watt, FM
Schlessinger, J
Wagner, EF
机构：
[1] Res Inst Mol Pathol, A-1030 Vienna, Austria
[2] Imperial Canc Res Fund, London WC2A 3PX, England
[3] NYU Med Ctr, Dept Pharmacol, New York, NY 10016 USA
来源：
CELL | 2000年 / 102卷 / 02期
基金：
奥地利科学基金会;
关键词：
D O I：
10.1016/S0092-8674(00)00026-X
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 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.
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页码：211 / 220
页数：10
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