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Density-dependent regulation of epidermal growth factor receptor expression.

Previous studies have demonstrated that binding of peptide growth factors such as epidermal growth factor (EGF) decreases as cell density increases. We now report that binding of EGF to MDA 468 breast carcinoma cells is reduced as cells increase in density with time in culture. Cells at low density bound more EGF per cell than cells at higher density. The reduction of EGF binding was due to a reduction in receptor number. Metabolic labeling of MDA 468 cells with [35S]-methionine followed by immunoprecipitation of the EGF receptor (EGFR) indicated that the amount of total receptor protein was decreased. Using RNA blot hybridization, we found that high-density cells contained decreased amounts of EGFR transcripts. Northern analysis revealed that both the 10- and 5.6-kilobase mRNA transcripts encoding the EGFR were decreased. These data suggest that increasing cell density with time in culture results in modulation of EGFR content, with changes at the level of both protein and mRNA expression.