, Volume 24, Issue 3, pp 241-250

Protein kinase C isoform α overexpression in C6 glioma cells and its role in cell proliferation

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Summary

Previous studies from this laboratory have demonstrated that protein kinase C (PKC) enzyme activity is highly correlated with the proliferation rate of glioma cells, and that glioma cells of both human and rat origin have very high PKC enzyme activity when compared to non-malignant glia including astrocytes, the antecedents of most gliomas. In the present study, by contrasting the rat C6 glioma cells with non-malignant rat astrocytes, we have sought to determine whether the high PKC enzyme activity of glioma cells was due to the overexpression of a specific isoform of PKC. By Western blot analyses, both C6 glioma cells and astrocytes were found to express PKCα, β, δ, ɛ and ζ, but not γ. Enzyme activity measurements revealed that the elevated PKC activity of glioma cells compared to glia was calcium-dependent, thereby implicating abnormal activity of the α or β isoforms. On Western blots, when compared to astrocytes, glioma cells were determined to overexpress PKCa but not β. An antisense oligonucleotide to PKCα, directed at the site of initiation of translation, inhibited the proliferation rate of glioma cells when compared to cells treated with control oligonucleotides; PKC enzyme activity and PKCa protein expression were significantly reduced by the antisense treatment. These results suggest that the high PKC enzyme activity of glioma cells, and its correspondence with proliferation rate, is the result of overexpression of isozyme a. Targetting PKCa in glioma cells may provide a refinement of therapy of glioma patients, some of which are already showing clinical stabilization when treated with drugs with PKC-inhibitory effects.