Protein kinase C zeta isoform is critical for proliferation in human glioblastoma cell lines.
Previous studies have confirmed that proliferation in glioblastoma cell lines can be blocked by non-isoform specific protein kinase C (PKC) inhibitors, e.g calphostin C, staurosporine. However, the exact mechanism of PKC involvement is poorly understood. The aim of this study was to explore the role of specific PKC isoforms in the aberrant growth of glioblastoma. Identification of the isoform(s) critical for proliferation in glioblastoma would present a better target for the design of chemotherapeutic strategies. To this end, we screened expression on PKC isoforms in four human glioblastoma cell lines both when proliferating and in a quiescent state using western assays. PKC isoforms alpha, beta, betaII and zeta were found to be expressed in all cell lines. PKC epsilon was detected in three out of four cell lines and PKC eta was detected in one out of four cell lines. Quiescence of growth resulted in down-regulation of PKC epsilon. We examined the role of these isoforms by studying the effect of PKC isoform-specific inhibitors bisindolylmaleimide-I and Gö6976 on proliferation in a panel of four human glioblastoma cell lines. Inhibition of PKC alpha and epsilon had no effect on proliferation, suggesting that previous studies targeting PKC alpha may not be of therapeutic benefit. More significantly, it was shown that inhibition of PKC zeta blocked proliferation. This suggests that the inhibition of PKC zeta may be an important chemotherapeutic target for arresting growth in glioblastoma.
Donson
A M
AM
Department of Pediatrics, University of Colorado Health Sciences Center, Denver, USA.
Banerjee
A
A
Gamboni-Robertson
F
F
Fleitz
J M
JM
Foreman
N K
NK
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D015536:Down-Regulation; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D010641:Phenotype; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D020033:Protein Isoforms; D011493:Protein Kinase C