REDUCED EXPRESSION OF NEUROFIBROMIN IN HUMAN MENINGIOMAS

Meningiomas are common, mostly benign, tumours arising from leptomenin geal cells of the meninges, which frequently contain mutations in the neurofibromatosis type 2 (NF2) gene. In this study, we analysed a prot ein product of the neurofibromatosis type 1 (NF1) gene, neurofibromin, in human established leptomeningeal cells LTAg2B, in 17 sporadic meni ngiomas and in a meningioma from a patient affected by NF2. The expres sion level of neurofibromin was determined by immunoblotting and immun oprecipitation with anti-neurofibromin antibodies. The functional stat us of neurofibromin was analysed through its ability to stimulate the intrinsic GTPase activity of p21 ras. In the cytosolic extracts of fou r sporadic meningiomas and in the NF2-related meningioma, the expressi on level and the GTPase stimulatory activity of neurofibromin were dra stically reduced compared with the lever present in the human brain, h uman established leptomeningeal cells LTAg2B and the remaining 13 meni ngiomas. Our results suggest that neurofibromin is expressed in leptom eningeal cells LTAg2B and in most meningiomas, i.e. tumours derived fr om these cells. The reduced expression and GTPase stimulatory activity of neurofibromin was found in about 23% of meningiomas and in the sin gle NF2-related meningioma analysed. These results suggest that decrea sed levels of neurofibromin in these tumours may contribute to their t umorigenesis.