TRANSFORMING GROWTH-FACTOR-BETA-1 HAS BOTH PROMOTING AND INHIBITING EFFECTS ON INDUCTION OF DNA-SYNTHESIS IN HUMAN FIBROBLASTS

Growth-arrested human normal fibroblasts, TIG-1, initiated DNA synthesis following addition of epidermal growth factor (EGF). Transforming growth factor-beta 1 (TGF-beta 1) by itself had no effect on induction of DNA synthesis. When EGF and TGF-beta 1 were added simultaneously to growth-arrested TIG-1 cells, induction of DNA synthesis was enhanced compared with that by EGF alone. Contrarily, when TGF-beta 1 was added earlier than 2 h or later than 2 h of EGF addition, induction of DNA synthesis was prevented, Induction of DNA synthesis by EGF was insensitive to pertusis toxin (PT, an inhibitor of Gi protein) and to staurosporine (a protein kinase inhibitor). The promoting effect of TGF-beta 1 on DNA synthesis was PT-insensitive and staurosporine-sensitive, Contrarily, inhibitory activity of TGF-beta 1 on DNA synthesis was PT-sensitive and staurosporine-insensitive, These studies suggest that the effect of TGF-beta 1 is to promote or to inhibit induction of DNA synthesis by EGF expressed through different signal transduction processes in the same cell. (C) 1995 Academic Press, Inc.