Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells.

作者：Tomoyuki Kawamoto, John M. Mendelsohn, Anh Dũng Lê, GORDON H. SATO, Cheri S. Lazar, Gordon N. Gill · 发表于：Journal of Biological Chemistry · 年份：1984 · DOI：10.1016/s0021-9258(17)42858-4 · 被引用次数：243 · 研究领域：HER2/EGFR in Cancer Research、Cancer Treatment and Pharmacology、Cancer Cells and Metastasis

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.