Protein kinase C activity correlates with the growth rate of malignant gliomas: Part II. Effects of glioma mitogens and modulators of protein kinase C.

Abstract

The proliferation rates of gliomas may be modulated by the protein kinase C (PKC) signal transduction system. The present study was undertaken to further examine the role of PKC system in growth regulation of gliomas in vitro by measurement of PKC activity over various phases of tumor growth and by assessing its potential role as a signal transduction system induced by serum mitogens and the known glioma mitogens epidermal growth factor and fibroblast growth factor. All human glioma lines examined, and the rat glioma C6, displayed high PKC activity relative to nonmalignant glial cells, which correlated with their proliferation rates over their respective growth phase. Frozen surgical human malignant glioma specimens also displayed high PKC activity. The relatively selective PKC inhibitor staurosporine (SP) reduced PKC activity and corresponding growth rates in a dose-related manner. Stimulation of PKC with phorbol esters under different concentrations of serum in the growth medium indicated that the high PKC activity, which correlated with their rapid growth rates, is highly susceptible to down-regulation by these agents. Epidermal growth factor and fibroblast growth factor increased both PKC activity and the growth rate of glioma line A172; addition of SP reduced the growth rate to levels observed in SP-treated control tumors, indicating that PKC may be a common signal transduction system induced by these mitogens. These results implicate PKC as an important signal transduction system regulating glioma growth, and offers a potential target for tumor inhibition.