TGF beta inhibits Go/S-phase transition in primary fibroblasts. Loss of response to the antigrowth effect of TGF beta is observed after immortalization

Transforming growth factor beta (TGF beta) may act as a negative growth regulator in secondary cultures of rodent fibroblasts by preventing quiescent cells from re-entering the cell cycle. Although TGF beta inhibits the serum induced transition from the Go to the S phase it does not inhibit induction of fos, myc, and JE. Actively growing cells are also inhibited in their proliferation by picomolar amounts of TGF beta. In contrast several established cell lines are not inhibited by TGF beta and in these it can cause quiescent cells to resume proliferation. This resistance to TGF beta can be traced back to the early divisions of immortal cells emerging from a senescence crisis, suggesting that alterations in the response of normal fibroblasts to TGF beta are concurrent with an unlimited proliferative potential. Induction of DNA synthesis by TGF beta is preceded in 5 established cell lines by induction of PDGF B chain mRNA as well as of other mRNAs associated with cell replication such as fos, myc, and JE. None of these genes is induced by TGF beta alone in presenescent cells. These results indicate that TGF beta can negatively regulate growth of normal presenescent fibroblasts. Alterations in the responsiveness to TGF beta can be detected immediately after immortalization which may contribute to the increased proliferative potential of these cells.