Epidermal growth factor-urogastrone action: induction of 2',5'-oligoadenylate synthetase activity and enhancement of the mitogenic effect by anti-interferon antibody.

Epidermal growth factor-urogastrone (EGF-URO), early in the course of stimulating DNA synthesis in quiescent human fibroblasts, also causes a three to five-fold elevation of the activity of intracellular 2',5'-oligoadenylate synthetase (2,5A synthetase), an enzyme that has been previously implicated in the antiproliferative effects of interferon. The increase in synthetase activity precedes DNA synthesis by approximately six hours, with maximal synthetase activity either preceding or coinciding with maximal DNA synthesis. EGF-URO stimulation does not result in the secretion of detectable amounts of interferon (IFN) into the growth medium and anti-human IFN-beta antibodies do not block the EGF-URO-mediated rise in 2,5A synthetase activity. Thus, the elevation of 2,5A synthetase can be attributed to the action of EGF-URO itself, and not to IFN. Nonetheless, in the presence of anti-human interferon-antibodies, the time course of EGF-URO-stimulated DNA synthesis is prolonged both in human and in Syrian hamster embryo fibroblasts; the effects of the antibody were reversed in both cell strains by the addition of human IFN-beta (HuIFN-beta). The data suggest a role for 2',5'-oligoadenylate synthetase in the process of EGF-URO-mediated mitogenesis and point to the possible production of interferon-related cell-associated regulators during the course of EGF-URO action.