Involvement of protein kinase C in growth regulation of human meningioma cells.
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.
Todo
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Department of Neurosurgery, International Medical Center of Japan, Tokyo.
Fahlbusch
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D000470:Alkaloids / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008577:Meningeal Neoplasms / Q000503:physiopathology*; D008579:Meningioma / Q000503:physiopathology*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D019311:Staurosporine; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology*
D000470:Alkaloids; D010703:Phorbol Esters; D011493:Protein Kinase C; D019311:Staurosporine