Differential regulation and expression of jun, c-fos and c-myc proto-oncogenes during mouse liver regeneration and after inhibition of protein synthesis.

In order to obtain information in vivo about the possible relationships between early response gene products, we have analysed the expression of c-myc, c-fos and jun proto-oncogenes in regenerating mouse liver. We show that c-myc, c-fos, jun B, c-jun and jun D mRNA expression is transiently increased soon after partial hepatectomy, jun and fos expression being induced earlier (30 min) than that of c-myc (1-2 h). C-fos, jun B and c-jun mRNA expression is dramatically enhanced (50 fold) while that of jun D and c-myc is weaker (less than 10 fold), but lasts longer. Moreover, the relative contributions of transcriptional and post-transcriptional regulations are unique for each proto-oncogene analysed. These results suggest that following the growth signal delivered by partial hepatectomy, the five proto-oncogenes analysed are all involved in the progression of hepatocytes through G1; however, due to their differential regulation and kinetics, they might play different roles in the changes in gene expression that occur during the transition from quiescence to proliferation. When protein synthesis is inhibited by injection of cycloheximide, the expression of c-myc, c-fos, jun B, c-jun and jun D mRNA is also transiently increased. Although this increase is mainly due to post-transcriptional mechanisms, c-myc, c-jun, jun D and, to a lesser extent, jun B transcription is enhanced, suggesting that labile repressor-like molecules may inhibit transcription of these genes in the quiescent liver. Moreover, the kinetics of c-myc, c-fos and jun mRNA induction are not identical, showing that different components are involved in their turnover or stability.