Cell Growth & Differentiation, Vol 7, Issue 2 173-178, Copyright © 1996 by American Association of Cancer Research

ARTICLES

Epidermal growth factor-induced apoptosis in A431 cells can be reversed by reducing the tyrosine kinase activity

LF Gulli, KC Palmer, YQ Chen and KB Reddy
Department of Pathology, Wayne State University, Detroit, Michigan 48201, USA.

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 to inhibition of cell proliferation and morphological features of apoptosis. However, at a lower concentration of EGF (0.01 nM), there is a 2-fold increase in EGF-R autophosphorylation and increased cell proliferation when compared to untreated cells. EGF treatment is associated with increased expression of c-myc and decreased expression of mutant p53 and p21/WAF protein. When A431 cells were simultaneously treated with 10 nM EGF and EGF-R antibody, there was a significant reduction in EGF-R autophosphorylation that was associated with increased cell proliferation. Based on these results, we postulate that overexpression of EGF-R could allow for selective growth advantage for tumor cells in the presence of normal or decreased ligand availability. However, excessive ligand binding would result in deregulated growth signaling, leading to growth inhibition and programmed cell death.

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