EGF RECEPTOR SIGNALING INHIBITS KERATINOCYTE APOPTOSIS - EVIDENCE FORMEDIATION BY BCL-X-L

Signaling through the epidermal growth factor receptor (EGFR) has been primarily implicated in the growth of epithelial cells including kera tinocytes. However, the mechanism by which EGFR stimulation promotes k eratinocyte cell growth is poorly understood, Here we report that huma n keratinocytes undergo apoptosis when incubated with the blocking EGF R monoclonal antibody 225 IgG, or PD153035, a highly specific EGFR tyr osine kinase inhibitor, Endogenous mRNA and protein levels of Bcl-X-L, a member the Bcl-2 family which suppresses apoptosis, were specifical ly inhibited by EGFR blockade, Furthermore, stimulation of EGFR signal ing through two natural ligands, transforming growth factor (TGF)-alph a and epidermal growth factor (EGF), increased the expression of Bcl-X -L in quiescent keratinocytes and HaCaT cells, Finally, ectopic expres sion of Bcl-X-L in HaCaT cells increased survival after EGFR blockade when compared to untransfected cells or HaCaT keratinocytes transfecte d with empty vector. These results suggest that the anti-apoptotic pro tein Bcl-X-L plays an important role in the maintenance of keratinocyt e survival in response to EGFR signaling.