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

Chemotherapeutic drugs that damage DNA kill tumor cells, in part, by induci ng the expression of a death receptor such as Fas or its ligand, FastL. Her e, we demonstrate that epidermal growth factor (EGF) stimulation of T47D br east adenocarcinoma and embryonic kidney epithelial (HEK293) cells protects these cells from Fas-induced apoptosis. EGF stimulation of epithelial cell s also inhibited Fas-induced caspase activation and the proteolysis of sign aling proteins downstream of the EGF receptor, Cbl and Akt/protein kinase B (Akt), EGF stimulation of Akt kinase activity blocked Fas-induced apoptosi s. Expression of activated Akt in MCF-7 breast adenocarcinoma cells was suf ficient to block Fas-mediated apoptosis, Inhibition of EGF-stimulated extra cellular signal-regulated kinase (ERK) activity did not affect EGF protecti on from Fas-mediated apoptosis. The findings indicate that EGF receptor sti mulation of epithelial cells has a significant survival function against de ath receptor-induced apoptosis mediated by Akt.