Interferon inhibition of bombesin-stimulated mitogenesis in Swiss 3T3 cells occurs without blocking c-fos and c-myc expression.

We have investigated the effect of murine interferon-beta on the growth of quiescent Swiss 3T3 cells stimulated by the amphibian tetradecapeptide mitogen bombesin. We found that IFN inhibited mitogenesis in bombesin-stimulated cells in a dose-dependent manner. In addition, bombesin, in common with platelet-derived growth factor (PDGF), was able to reverse the inhibitory effects of IFN in cells stimulated by epidermal growth factor (EGF) and insulin, which elicit a mitogenic response via a distinct signaling pathway. The observation that IFN was as effective in inhibiting DNA synthesis when added 48 h before or as late as 3 h after the mitogen, indicated that a block in one of the early regulatory signals was not essential for the anti-growth effects. Indeed, IFN did not inhibit the increased expression of c-fos and c-myc mRNA induced by bombesin in quiescent Swiss 3T3 cells. The combined data indicate that events occurring late in G1 are more likely targets for IFN action in Swiss 3T3 cells.