Involvement of protein kinase C in growth regulation of human meningioma cells

Abstract

In order to investigate the possible role of protein kinase C (PKC)-mediated signal pathways in growth regulation of meningiomas, we examined the effect of two PKC-activating phorbol esters, 12-O-tetradecanoyl-13-phorbol acetate (TPA) and phorbol 12, 13-dibutyrate (PDBu), and PKC inhibitor, staurosporine, on cell proliferation using low-passage human meningioma cells in culture. TPA (0.1 to 100 ng/ml) caused a dose-dependent stimulation of cell proliferation in six of eight meningioma cultures. At optimal concentrations of TPA, the cell growth ranged from 113% to 251% versus control. In contrast, PDBu (0.1 to 100 ng/ml) caused a significant inhibition of cell proliferation in three of five meningioma cultures. At optimal concentrations of PDBu, the cell growth ranged from 52% to 79% of control. Staurosporine exhibited a stimulation of cell proliferation (135% to 178%) in three of four meningioma cultures studied at a concentration of 10(-10) to 10(-9)M, although a tendency of growth inhibition was observed at a lower concentration. A time course of DNA synthesis in response to TPA, assessed by [3H] thymidine incorporation studies, revealed a time- and dose-dependent stimulation and/or inhibition which further depended on the serum concentration of the growth medium used. The overall results indicate that PKC-mediated signal pathways are closely involved in growth regulation of human meningioma cells. The results further suggest that the signalling processes consist of complex mechanisms which await to be elucidated.