The Growth-Inhibitory Block of TGF-β Is Located Close to the G1/S Border in the Cell Cycle

Abstract

Transforming growth factor-β (TGF-β) inhibits DNA synthesis in dense cultures of young human embryonic fibroblasts and antagonizes the mitogenic action of platelet-derived growth factor (PDGF). The inhibition of the PDGF-BB action by TGF-β was independent of the induction of mRNAs for the PDGF-A chain and PDGF-β receptor, the predominant types of PDGF receptor in human fibroblasts. The TGF-β-mediated inhibition did not influence the expression of various genes that are involved in the transition from the arrested (G0) state to the S phase of the cell cycle. Indeed, TGF-β upregulated the "early" genes c-myc, c-fos, and jun B and downregulated the growth arrest-specific (gas) genes. These results suggest that the inhibition of DNA synthesis by TGF-β in human fibroblasts is independent of modulation of expression of early and gas genes, placing the TGF-β block comparatively late in the G0 to S transition. In cultures of senescent human fibroblasts TGF-β stimulated DNA synthesis but, nevertheless, had the same effect as in young cells on the expression of PDGF chains and receptor genes, as well as on early and gas genes, with the exception of a significantly lower induction of c-fos.