title: Effects of retinoic acid on the binding and mitogenic activity of epidermal growth factor.
abstract: In this study the effects of retinoic acid on the binding and mitogenic activity of epidermal growth factor (EGF) in mouse fibroblast Balb/c 3T6 cells are further examined. Retinoic acid treatment of 3T6 cells results in a sixfold enhancement of 125I-labeled mouse EGF binding when assayed at 37 degrees C. In both retinoic acid-treated and control cells, cell-associated 125I-EGF is rapidly internalized, degraded, and secreted. Retinoic acid treatment does not seem to have a significant effect on the rate of internalization and degradation of EGF. At 0 degrees C, internalization of EGF is strongly inhibited in both retinoic acid-treated and control cells. Under these conditions retinoic acid-treated cells still exhibit a tenfold higher level of EGF binding compared to control cells. When exposed to high concentrations of EGF both retinoic acid-treated and control cells "down-regulate" their EGF receptors. And although the growth rate of retinoic acid-treated cells is about half that of control cells, the rate at which EGF binding capacity is restored after down-regulation is about three times as fast as in control cells. No direct antagonism on EGF binding was observed between the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and retinoic acid. EGF is a potent mitogen for 3T6 cells in serum-free medium; retinoic acid inhibits the mitogenic activity of EGF even though it increases EGF binding. Retinoic acid also inhibits cell proliferation induced by sarcoma growth factor (SGF) and insulin.
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors; D006133:Growth Substances / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015291:Transforming Growth Factors; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D006133:Growth Substances; D007328:Insulin; D008934:Mitogens; D010455:Peptides; D011956:Receptors, Cell Surface; D014212:Tretinoin; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate