Search

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.

Rat glial cells were grown in tissue culture in vitamin B12-deficient medium. As the intracellular level of coenzyme B12 decreased, the cells made increasing amounts of two unusual fatty acids. The fatty acids were unbranched acids with 15 and 17 carbon atoms and arose as the cells progressively lost the ability to metabolize propionic acid through the B12-requiring methylmalonyl-CoA mutase reaction. The levels of the 15- and 17-carbon acids returned to normal when the cultures were supplemented with vitamin B12. The possible importance of similar fatty acid changes in human vitamin B12 deficiency and in disorders of 3- and 4- carbon acid metabolism is speculated.