Effect of epidermal growth factor on ornithine decarboxylase activity in A431 cells.

Epidermal growth factor (EGF) stimulates mitogenesis in a number of cell lines; but in A431 cells, EGF causes inhibition of replication. To investigate the possibility that an alteration in the polyamine biosynthetic pathway could be associated with this unusual response of A431 cells to EGF, we evaluated the effect of EGF on ornithine decarboxylase activity. We also evaluated the action of inhibitors of ornithine decarboxylase (difluoromethyl ornithine and retinoic acid) on A431 cell replication. We found a significant stimulatory effect of EGF on ornithine decarboxylase activity and a significant inhibition of cell replication by ornithine decarboxylase inhibitors. These findings are suggestive that the paradoxical response of A431 cells to EGF stimulation is not due to an aberrant response in polyamine formation. Specifically, we found that A431 cells respond, like other cell types, to a growth factor (viz., EGF) with an increase in ODC activity. Moreover, in A431 cells ornithine decarboxylase activity is required for replication.