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 synthes is following addition of epidermal growth factor (EGF). Transforming g rowth 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 insensi tive to pertusis toxin (PT, an inhibitor of Gi protein) and to stauros porine (a protein kinase inhibitor). The promoting effect of TGF-beta 1 on DNA synthesis was PT-insensitive and staurosporine-sensitive, Con trarily, inhibitory activity of TGF-beta 1 on DNA synthesis was PT-sen sitive and staurosporine-insensitive, These studies suggest that the e ffect of TGF-beta 1 is to promote or to inhibit induction of DNA synth esis by EGF expressed through different signal transduction processes in the same cell. (C) 1995 Academic Press, Inc.