TRANSFORMING GROWTH FACTOR-BETA-1-INDUCED DELAY OF CELL-CYCLE PROGRESSION AND ITS ASSOCIATION WITH GROWTH-RELATED GENE-EXPRESSION IN MOUSE FIBROBLASTS

TGFbeta-induced cell cycle progression is relatively slower than that induced by EGF or PDGF-BB. Further, TGFbeta delays EGF or PDGF-induced 5-phase entry in C3H 10T1/2 mouse fibroblasts. In accordance with thi s delay, the induction of mRNA level of 'immediate early genes' such a s c-myc, c-fos, c-jun and junB by TGFbeta has slower kinetics compared with those of EGF. TGFbeta induces c-sis gene, suggesting possible in volvement of secondary growth stimulation by PDGF-like proteins. Howev er, anti-PDGF-AB antibody, which was inhibitory to FDGF-BB-induced [H- 3]thymidine incorporation, did not block TGFbeta-induced DNA synthesis . These results first demonstrate that the delay of cell cycle progres sion by TGFbeta is closely associated with the altered regulation of g rowth-related gene expression in fibroblasts.