C-MYC-INDUCED APOPTOSIS IN FIBROBLASTS IS INHIBITED BY SPECIFIC CYTOKINES

We have investigated the mechanism by which deregulated expression of c-Myc induces death by apoptosis in serum-deprived fibroblasts. We dem onstrate that Myc-induced apoptosis in low serum is inhibited by a res tricted group of cytokines, principally the insulin-like growth factor s and PDGF. Cytokine-mediated protection from apoptosis is not linked to the cytokines' abilities to promote growth. Protection from apoptos is is evident in the post-commitment (mitogen-independent) S/G(2)/M ph ases of the cell cycle and also in cells that are profoundly blocked i n cell cycle progression by drugs. Moreover, IGF-I inhibition of apopt osis occurs in the absence of protein synthesis, and so does not requi re immediate early gene expression. We conclude that c-Myc-induced apo ptosis does not result from a conflict of growth signals but appears t o be a normal physiological aspect of c-Myc function whose execution i s regulated by the availability of survival factors. We discuss the po ssible implications of these findings for models of mammalian cell gro wth in vivo.