Epidermal Growth Factor-Induced Down-Regulation of Receptor Does Not Occur in HeLa Cells Grown in Defined Medium

125I-Labeled epidermal growth factor (EGF) binds to HeLa cells in culture under completely defined conditions in a specific and saturable manner. When the cultures are maintained in serum, all the reported phenomena of down-regulation occur. In contrast, in cultures maintained in serum-free hormone-supplemented medium, binding is maximal after 50 min and remains constant for at least 18 hr. EGF retains its mitogenic activity in this defined system; as little as 4 pM EGF elicits a 2-fold increase in cell number in 5 days. EGF appears to be in reversible equilibrium with a constant number of surface receptors, and gel filtration analysis indicates a decrease in the rate of degradation and release of bound125I-labeled EGF. These results indicate that EGF can retain its mitogenic activity in the absence of concomitant downregulation.