DIFFERING ROLES OF PROTEIN-KINASE-C ON THE SIGNAL-TRANSDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA AND FACTOR-BETA ON PANC-1 CELLS - IN-VITRO AUTORADIOGRAPHIC INVESTIGATION

We investigated alterations in protein kinase C (PKC) activity of PANC -1 cells following treatment with tumour necrosis factor (TNF)-alpha o r TNF-beta by an in vitro autoradiographic method. Binding studies per formed on whole cells using [H-3]phorbol-12,13-dibutyrate (PDBu) as a ligand revealed strong activation of PKC by TNFs within 30 min. The ef fect was similar to that seen after 30 min treatment with 12-O-tetrade canoylphorbol-13-acetate (TPA). After treatment for 24 h, TNF-beta cau sed a marked down-regulation of PKC similar to that seen after 24 h tr eatment with TPA; significant activation persisted, however, in the ce lls treated for 24 h with TNF-alpha. Our data suggest that PKC activat ion may play a more important role in the TNF-alpha signal transductio n pathway than in that of TNF-beta.