Proto-Oncogene Expression and Proliferative Activity in Human Malignant Gliomas

Abstract

The identification of oncogene products that are highly expressed in malignant glial cells could permit its use both in the diagnosis and in the grading of malignant brain tumors. In this study monoclonal antibodies to the Ha-ras and c-myc gene products (i.e. p21 and p62 oncoprotein respectively) were used in conjunction with flow cytometry (FCM) to characterize and quantitate the oncoprotein expression in 2 human glioblastoma-derived primary cell lines, 5 fresh malignant gliomas and 2 nonneoplastic brain tisue biopsy sample. In these experiments, the levels of the p21 and p62 fluorescence (i.e. Ha-ras and c-myc oncogene expression) in the malignant cultured cells and in the brain tumors samples were more than three times that of the nonneoplastic cells. FCM was also used to relate the quantity of the Ha-ras and c-myc oncoproteins present in the cells to their cell cycle phase. In all neoplastic specimens (which showed diploid DNA content), there was an equal distribution of p21 in G0/ G1, S and G2-M phases of the cell cycle while, the p62 underwent a twofold increase as the cells progresed from G0/G1 to G2-M. The results support the hypotesis of Haras and c-myc activation in human glioblastomas, also, FCM permits a simultaneous examination of the cytokinetic characteristics of tumor cells and oncogene expression, providing a useful tool in the study of molecular biology of brain tumors.