OVEREXPRESSION OF PKC-XI IN NIH3T3 CELLS DOES NOT INDUCE CELL-TRANSFORMATION NOR TUMORIGENICITY AND DOES NOT ALTER NF-KAPPA-B ACTIVITY

Signal transduction is the major mechanism by which cells communicate among themselves through extracellular stimuli. Among the different St ructural components involved in signal transduction, protein kinases a re one of the key elements in the process. Protein kinase C is a multi member family of kinases which has been involved in the regulation of diverse cellular functions. Regulation of cell growth in fibroblasts h as been reported to be one of such functions, In particular the PKC ze ta isoenzyme has been postulated to be transforming to NIH3T3 cells (B erra et al., 1993) and to serve as an effector for Ras proteins throug h the regulation of the NF kappa B transcription factor (Dominguez et al., 1993) and direct interaction (Diaz-Meco et al., 1994). We have in vestigated the effects of overexpressing the mouse wild-type PKC zeta in NIH3T3 cells. When compared to the parental NIH3T3 cells, we have f ound (1) no significant effect on cell morphology; (2) no difference i n growth properties in the absence of serum or in the presence of indi vidual growth factors such as insulin, phorbol esters or PDGF; (3) no growth in soft agar nor tumorigenic activity in nude mice. In addition cells stably overexpressing the PKC zeta kinase did not interfere or amplify the induction of NF kappa B activity by tumor necrosis factor alfa (TNF-alpha) nor altered NF kappa B activity in transient expressi on of cells treated with TNF-alpha. Thus, mammalian PKC zeta is most l ikely not directly involved in the regulation of cell proliferation in fibroblasts nor affects directly or indirectly the activation of NF k appa B.