TRANSFORMING GROWTH-FACTOR BETA-1-MEDIATED INHIBITION OF SMOOTH-MUSCLE CELL-PROLIFERATION IS ASSOCIATED WITH A LATE G1 CELL-CYCLE ARREST

The effect of transforming growth factor beta1 (TGFbeta1) on the proli ferative response of aortic smooth muscle cells (SMC) in vitro was inv estigated. TGFbeta1 substantially inhibited the growth of human and bo vine SMC. Rapidly growing SMC and quiescent serum-stimulated SMC were inhibited by TGFbeta1 with an ID50 of approximately 0.5 ng/ml and maxi mal inhibition was observed at 10 ng/ml TGFbeta1 In the presence of TG Fbeta1, quiescent serum-stimulated SMC progress into the G1 phase of t he cell cycle, but become reversibly arrested at a point temporally lo cated 1-2 hours from S phase. Release from this late G1 TGFbeta1 arres t point results in S phase entry within 2 hours. Associated with this inhibitory effect is a decrease in the histone H1 kinase activity of p 34cdc2 protein kinase while TGFbeta1 has no effect on the transcriptio n or translation of p34cdc2. Under these growth inhibitory conditions, TGFbeta1 is still capable of upregulating the expression of fibronect in mRNA. These results suggest that TGFbeta1 growth inhibition in SMC is associated with the regulation of p34cdc2 activity in late G1. (C) 1993 Wiley-Liss, Inc.