DISPARITY IN EXPRESSION OF PROTEIN-KINASE-C-ALPHA IN HUMAN GLIOMA VERSUS GLIOMA-DERIVED PRIMARY-CELL LINES - THERAPEUTIC IMPLICATIONS

Intracellular signal transduction by the protein kinase C (PKC) family of enzymes plays a critical role in carcino-genesis and cellular grow th regulation. Recent studies have suggested that the PKC isoform alph a may be a critical target for antiglioma therapy in humans (G. H. Bal tuch et at., Can. J. Neurol. Sci., 22: 264-271, 1995). We studied the expression and subcellular distribution of the PKC alpha isoform in hu man high- and low-grade gliomas and also in glioma-derived cell lines with immunoblot analyses. Cell lines derived from high-grade gliomas e xpressed higher levels of PKC alpha than did cell lines derived from l ow-grade gliomas, In glioblastoma-derived cell lines, PKC a was mainly expressed in the soluble (cytosolic) fraction, indicating an inactive state of the enzyme. When analyzed in freshly frozen samples from hum an gliomas, the expression of PKC alpha was at similar levels in high- and low-grade tumors and was also similar to the levels in normal bra in tissue controls. The PKC partial antagonist bryostatin 1, currently undergoing Phase II testing in patients with malignant gliomas, was c apable of specifically down-regulating PKC alpha in vitro in glioblast oma-derived cell lines. However, this was not associated with signific ant growth inhibition. We conclude that the observed overexpression of PKC alpha in glioblastoma-derived cell lines may be an artifact of in vitro growth. Furthermore, we conclude that expression of PKC a in gl ioma-derived cell lines is not essential for cellular growth in vitro because down-regulation of PKC alpha following treatment with bryostat in 1 was not associated with growth inhibition.