The epidermal growth factor receptor is associated with phospholipase C-γ1 in meningiomas

In this study we evaluated phospholipase C-γ1 (PLC-γ1) expression, activity, and association with the epidermal growth factor (EGF) receptor in a series of human meningiomas as well as cultured meningioma cells. Phospholipase C-γ1 was detectable by immunoblot and immunohistochemistry in 13 of 13 meningioma specimens. Epidermal growth factor receptors were detected by immunoblot in six of nine meningiomas (67%) and by immunohistochemistry in 13 of 19 meningiomas (68%) but not in normal leptomeningeal cells. In two of three meningiomas EGF receptors and/or a 170-kd phosphotyrosine band precipitated with a PLC-γ1 antiserum. Both PLC-γ1 and EGF receptors also exhibited the same pattern of immunostaining on meningioma tissue sections. Phospholipase C-γ1 catalytic activity, measured in a PIP2 hydrolysis assay, was higher in nine EGF receptor-positive meningiomas than in six EGF receptor-negative meningiomas (P = .05; t test). Finally, treatment of cultured meningioma cells with transforming growth factor-α induced a 78% increase in PLC-γ1 catalytic activity. Thus, these data are consistent with the possibility that the EGF receptor tyrosine kinase regulates PLC-γ1 activity in native meningioma tissue.