Epidermal growth factor protects epithelial cells against Fas-induced apoptosis - Requirement for Akt activation

作     者：Gibson, S Tu, S Oyer, R Anderson, SM Johnson, GL 

作者机构：Univ Colorado Sch Med Program Mol Signal Transduct Div Basic SciNatl Jewish Med & Res Ctr Denver CO 80206 USA Univ Colorado Sch Med Dept Pathol Denver CO 80206 USA Univ Colorado Sch Med Dept Pharmacol Denver CO 80206 USA 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (J. Biol. Chem.)

年 卷 期：1999年第274卷第25期

页      面：17612-17618页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：NIDDK NIH HHS [DK 37871, DK 48845] Funding Source: Medline NIGMS NIH HHS [GM 30324] Funding Source: Medline 

摘      要：Chemotherapeutic drugs that damage DNA kill tumor cells, in part, by inducing the expression of a death receptor such as Fas or its ligand, FastL. Here, we demonstrate that epidermal growth factor (EGF) stimulation of T47D breast adenocarcinoma and embryonic kidney epithelial (HEK293) cells protects these cells from Fas-induced apoptosis. EGF stimulation of epithelial cells also inhibited Fas-induced caspase activation and the proteolysis of signaling proteins downstream of the EGF receptor, Cbl and Akt/protein kinase B (Akt), EGF stimulation of Akt kinase activity blocked Fas-induced apoptosis. Expression of activated Akt in MCF-7 breast adenocarcinoma cells was sufficient to block Fas-mediated apoptosis, Inhibition of EGF-stimulated extracellular signal-regulated kinase (ERK) activity did not affect EGF protection from Fas-mediated apoptosis. The findings indicate that EGF receptor stimulation of epithelial cells has a significant survival function against death receptor-induced apoptosis mediated by Akt.