125I-EGF binding to responsive and nonresponsive cells in culture: loss of cell-associated radioactivity relates to growth induction.

A comparison of the binding and overall processing of epidermal growth factor (EGF) was made in ten mammalian fibroblast-like and three epithelial-like cell lines. EGF stimulated the growth of five fibroblastic cell lines (132 to 224%) after 10 days in the constant presence of EGF and were termed "responsive". Eight of the lines did not respond or were growth inhibited by EGF (-64 to + 21%) and were listed as "nonresponsive". Both "responsive" and "nonresponsive" cell lines possessed specific saturable membrane receptors for EGF, but no consistent differences were found between the number of apparent receptors per cell or the concentrations of 125I-EGF required for half maximal binding. However, a consistent difference between the "responsive" and "nonresponsive" cell lines was observed when the amount of cell associated 125I-labeled EGF was measured as a function of incubation time at 37 degrees C in the constant presence of the hormone. In every cell line we classified as responsive, the binding of 125I-EGF reached a maximum after 30 minutes incubation at 37 degrees C and the cell associated radiolabel subsequently decreased by 42-68% within 4 hours. In contrast, the "nonresponsive" cell lines required 1-2 h to reach maximal binding and showed a minimal decrease of 1-10% during the 4-h period. These data indicate that a variety of different cell lines can possess receptors with similar binding properties but process EGF in a dissimilar manner. This difference in processing may reflect the specific events which are necessary for the induction of cell growth.