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.

引用

页码：211 / 220

页数：10

共 51 条

[1] MEMBRANE TARGETING OF THE NUCLEOTIDE EXCHANGE FACTOR SOS IS SUFFICIENT FOR ACTIVATING THE RAS SIGNALING PATHWAY [J].