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Overexpression of the Epidermal Growth Factor Receptor Contributes to Enhanced Ligand-Mediated Motility in Keratinocyte Cell Lines¹

Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611

Address all correspondence and requests for reprints to: Dr. Laurie G. Hudson, Department of Molecular Pharmacology and Biological Chemistry, Searle 8–565, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611.

In keratinocytes, epidermal growth factor (EGF) promotes cell motility in addition to proliferation. As EGF receptor expression is elevated during wound healing and in many epithelial tumors, we wanted to investigate whether there is a direct relationship between EGF receptor expression and ligand-mediated cellular locomotion. EGF receptor activation induced cell migration in normal keratinocytes and their tumorigenic counterparts; however, the rate of colony dispersion and in vitro reepithelialization was more rapid in the squamous cell carcinoma (SCC) lines that exhibited elevated (5-fold) EGF receptor levels. Within a single SCC line, submaximal concentrations of EGF or reduction of EGF receptor activity by an anti-EGF receptor neutralizing antibody resulted in delayed kinetics of in vitro reepithelialization. Thus, suppression of EGF receptor activity in an overexpressing SCC line restores a migratory response that more closely resembles that of normal keratinocytes. Conversely, ligand-induced colony dispersion was augmented in stable clonal cell lines in which EGF receptor expression was elevated after introduction of an EGF receptor complementary DNA construct. Collectively, these findings suggest that the migratory potential of keratinocytes is modulated at the level of both receptor expression and ligand concentration, with a positive correlation between EGF receptor levels and ligand-induced cell motility.

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