Retinoic acid-induced changes in epidermal growth factor binding and in biological responses mediated by phorbol ester tumor promoter

We investigated the ability of retinoic acid (RA) to alter the binding of epidermal growth factor (EGF) to Rat-1 and Swiss mouse 3T3 cells, the EGF-related induction of ornithine decarboxylase (ODC) activity and DNA synthesis. Pretreatment of 3T3 cells with 10^-10-10^-5 M RA produced a dose-dependent increase in EGF binding. The increased EGF binding appeared to result from an increased number of EGF receptors and did not occur in Rat-1 cells which, unlike 3T3 cells, possessed measureable amounts of cellular retinoic acid binding protein (CRABP). Both cell lines responded to RA pretreatment with an increase in EGF- and TPA-induced ODC activity, without a concomitant increase in DNA synthesis in either cell line. We suggest that the increase in EGF binding induced by RA in 3T3 cells is apparently unrelated to alterations in EGF-induced biological responses and to the presence of CRABP.