TUMORIGENICITY OF MTG8, A LEUKEMIA-RELATED GENE, IN CONCERT WITH V-HA-RAS GENE IN BALB 3T3 CELLS/

The MTG8 (ETO) gene has been identified as the translocation partner o f AML1 (PEBP2 alpha B or CBF alpha 2) gene in the AML7/MTG8 (ETO) fuse d gene caused by t(8;21) translocation in human acute myeloid leukaemi a, M2 type. Although AML1/MTG8 chimaeric protein is known to inhibit t he functioning of AML1 protein, the precise function of MTG8 gene itse lf is not known yet. We studied the significance of MTG8 gene in the o ncogenicity of AML1/MTG8 fused gene, by introducing full-length MTG8 c DNA into both BALB/3T3 cells containing v-Ha-ms gene (Bhas 42 cells) a nd BALB/3T3 cells without v-Ha-ras gene. Irrespective of the overexpre ssion of MTG8 gene in both groups of cells, Bhas-MTG8 clones which con tained v-Ha-ras gene and expressed the MTG8 gene at a level more than twice that of parental Bhas 42 cells induced cell transformation, wher eas BALB-MTG8 clones without v-Ha-ras gene did not. Furthermore, injec tion of the transformed Bhas-MTG8 clones into the subcutaneous tissue of nude mice induced tumours, whereas that of BALB-MTG8 clones did not . These results suggest that MTG8 gene product, in cooperation with vi ral Ras protein, resulted in tumour formation. We provide the first ev idence that MTG8 gene by itself has a carcinogenic property within the AML1/MTG8 (ETO) fused gene.