A. Zellner et al., DISPARITY IN EXPRESSION OF PROTEIN-KINASE-C-ALPHA IN HUMAN GLIOMA VERSUS GLIOMA-DERIVED PRIMARY-CELL LINES - THERAPEUTIC IMPLICATIONS, Clinical cancer research, 4(7), 1998, pp. 1797-1802
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.