Interferon Inhibition of Bombesin-Stimulated Mitogenesis in Swiss 3T3 Cells Occurs Without Blocking c- fos and c- myc Expression

Abstract

We have investigated the effect of murine interferon-β 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.