DIFFERENTIAL EXPRESSION OF MYC, MAX AND RB1 GENES IN HUMAN GLIOMAS AND GLIOMA CELL-LINES

Deregulated expression of myc proto-oncogenes is implicated in several human neoplasias. We analysed the expression of c-myc, N-myc, L-myc, max and RBI mRNAs in a panel of human gliomas and glioma cell lines an d compared the findings with normal neural cells. The max and RB1 gene s were included in the study because their protein products can intera ct with the Myc proteins, being thus putative modulators of Myc activi ty. Several gliomas contained c/L-myc mRNAs at levels higher than thos e in fetal brain, L-myc predominantly in grade II/III and c-myc in gra de III gliomas. High-level N-myc expression was detected in one small- cell glioblastoma and lower levels in five other gliomas. In contrast, glioma cell lines totally lacked N/L-myc expression. The in situ hybr idisations revealed mutually exclusive topographic distribution of myc and glial fibrillary acidic protein (GFAP) mRNAs, and a lack of corre lation between myc expression and proliferative activity. max and RBI mRNAs were detected in most tumours and cell lines. The glioma cells d isplayed interesting alternative splicing patterns of max mRNAs encodi ng Max proteins which either suppress (Max) or augment (Delta Max) the transforming activity of Myc. We conclude that (1) glioma cells in vi vo may coexpress several,nye genes, thus resembling fetal neural cells ; but (2) cultured glioma cells expression only c-myc; (3) myc, max an d RBI are regulated independently in glioma cells; and (4) alternative processing of max mRNA in some glioma cells results in Delta Max enco ding mRNAs not seen in normal fetal brain.