THE EFFECTS OF THE INSULIN-LIKE GROWTH-FACTORS AND TRANSFORMING GROWTH-FACTOR-BETA ON THE JUN PROTOONCOGENE FAMILY IN MC3T3-E1 CELLS

Previous studies have demonstrated that when cells of the mouse osteob lastic cell line MC3T3-E1 are exposed to IGF-I and IGF-II they exhibit rapid and transient induction of the transcript from the proto-oncoge ne c-fos [8]. To clarify the relationship between induction of cell pr oliferation and proto-oncogene expression in MC3T3-E1 cells, the acute affects of IGF-I and IGF-II, growth factors that stimulate cell proli feration, and of TGF-beta 1, which inhibits cell proliferation, northe rn analyses with cDNA-derived probes for the proto-oncogenes c-jun,jun -B, and jun-D were undertaken. Concurrent northern analyses with a pro be for c-fos extended our previous results to include the effect of TG F-beta 1 on c-fos. IGF-I does not induce the c-jun, jun-B, or jun-D tr anscripts, the former and latter being produced at detectable levels c onstitutively. After 1 hour of exposure to IGF-II the c-jun transcript response ranges from onefold to 13-fold and the jun-D transcript resp onse ranges around twofold. After 1 hour of exposure to TGF-beta 1, th e jun-B transcript response ranges from eightfold to 24-fold, the c-fo s transcript response ranges between sixfold and sevenfold. The differ ences observed in the magnitude and kinetics of the induction provoked by these growth factors is consistent with the presence of a regulato ry circuit acting through the Jun family members which may act to stim ulate transcription differentially when bound to DNA either as homodim ers or, with Fos family proteins, as heterodimers.