EPIDERMAL GROWTH FACTOR-INDUCED APOPTOSIS IN A431 CELLS CAN BE REVERSED BY REDUCING THE TYROSINE KINASE-ACTIVITY

A431 cells overexpress epidermal growth factor receptors (EGF-Rs) and are inhibited by EGF, We show that treatment of A431 cells with 10 nM EGF induced a 15-fold increase in EGF-R autophosphorylation, leading t o inhibition of cell proliferation and morphological features of apopt osis, However, at a lower concentration of EGF (0.01 nM), there is a 2 -fold increase in EGF-R autophosphorylation and increased cell prolife ration when compared to untreated cells, EGF treatment is associated w ith increased expression of c-myc and decreased expression of mutant p 53 and p21/WAF protein. When A431 cells were simultaneously treated wi th 10 nM EGF and EGF-R antibody, there was a significant reduction in EGF-R autophosphorylation that was associated with increased cell prol iferation, Based on these results, we postulate that overexpression of EGF-R could allow for selective growth advantage for tumor cells in t he presence of normal or decreased ligand availability, However, exces sive ligand binding would result in deregulated growth signaling, lead ing to growth inhibition and programmed cell death.