PKC-DEPENDENT AND PKC-INDEPENDENT CELLULAR EFFECTS INDUCED BY RECOMBINANT TRANSFORMING GROWTH-FACTOR TYPE-BETA-1

TGF-beta 1 purified from human platelets induces colony formation of rat fibroblasts reversibly when administered together with EGF. TGF-beta 1 has been reported by us to lead to stable transformation of rat fibroblasts, to activate latent Epstein-Barr virus, to exhibit tumor promoting activity for murine fibroblasts, and to cause the release of apoptosis-inducing signals from normal cells which are directed specifically against transformed cells. The use of recombinant TGF-beta 1 in this study showed that all the effects measured were indeed due to TGF-beta 1. In order to get information on intracellular signal pathways induced by TGF-beta 1, specific inhibitors of protein kinase C (PKC) were applied. Induction of EBV antigens by TGF-beta 1 was dependent on the function of PKC, whereas induction of apoptosis in transformed cells by TGF-beta 1-treated normal cells was independent of the action of PKC.