Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells.
The relation between the concentration of epidermal growth factor (EGF) receptor/kinase and effects of EGF on cell proliferation has been studied using variant A431 cells and antagonist anti-EGF receptor monoclonal antibodies. Clonal A431 cell variants selected for escape from the EGF-mediated growth inhibition of parental A431 cells all have reduced concentrations of EGF receptor/kinase; Harvey sarcoma virus-transformed A431 cells, which have escaped from EGF-mediated growth inhibition, also have reduced EGF receptors. Three clonal variants which have reacquired EGF-mediated growth inhibition have 2- to 4-fold more EGF receptor than their respective parent variant. A biphasic response with stimulation at low and inhibition at high concentrations of EGF was especially evident in revertants of clone 29. Three separate antagonist monoclonal anti-EGF receptor antibodies block the growth inhibitory effects of EGF and uncover EGF-mediated growth stimulation. These studies indicate that in A431 cell variants a continuum of ligand-activated EGF receptors determines proliferative responses from low concentrations of active receptors under basal conditions to intermediate concentrations causing growth stimulation to high concentrations, causing inhibition of cell proliferation.
D000911:Antibodies, Monoclonal; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D066246:ErbB Receptors; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D011494:Protein Kinases; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases