Overexpression of PKC zeta 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 structural components involved in signal transduction, protein kinases are one of the key elements in the process. Protein kinase C is a multimember family of kinases which has been involved in the regulation of diverse cellular functions. Regulation of cell growth in fibroblasts has been reported to be one of such functions. In particular the PKC zeta isoenzyme has been postulated to be transforming to NIH3T3 cells (Berra et al., 1993) and to serve as an effector for Ras proteins through the regulation of the NF kappa B transcription factor (Dominguez et al., 1993) and direct interaction (Díaz-Meco et al., 1994). We have investigated the effects of overexpressing the mouse wild-type PKC zeta in NIH3T3 cells. When compared to the parental NIH3T3 cells, we have found (1) no significant effect on cell morphology; (2) no difference in growth properties in the absence of serum or in the presence of individual 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 expression of cells treated with TNF-alpha. Thus, mammalian PKC zeta is most likely not directly involved in the regulation of cell proliferation in fibroblasts nor affects directly or indirectly the activation of NF kappa B.
Montaner
S
S
Instituto de Investigaciones Biomédicas, CSIS, Madrid, Spain.
Ramos
A
A
Perona
R
R
Esteve
P
P
Carnero
A
A
Lacal
J C
JC
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D015870:Gene Expression; D006133:Growth Substances / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D011493:Protein Kinase C / Q000235:genetics*; D015398:Signal Transduction; D000099221:Protein Kinase C zeta
D006133:Growth Substances; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta