A Specific Chromosome Change and Distinctive Transforming Genes Are Necessary for Malignant Progression of Spontaneous Transformation in Cultured Chinese Hamster Embryo Cells

Chinese hamster embryo (CHE) cell strains, each initiated from a separate cell stock obtained from different mothers, were transferred successively at intervals of 3 days and the changes in growth properties and karyotypes at various passages were examined. All nine cell strains proliferated at varying growth rates for 60 passages but only 2 (designated CHE A1 and CHE A2) of them expressed malignant phenotypes. The acquisition of tumorigenicity in nude mice was observed in CHE A1 and CHE A2 cells at passages 40 and 10, respectively. After 5 passages, 8 of 9 cell strains contained one or two common additional chromosomes, chromosome 3q and/or chromosome 5, although one cell strain (designated CHE A3) maintained a normal diploid karyotype for 60 passages. Trisomy of chromosome 3q was observed in all tumorigenic CHE A1 and A2 cells. One or two 3q chromosomes were detected in all tumor‐derived cell lines established from tumors produced by these tumorigenic cells. DNA from tumorigenic cells and tumor‐derived cell lines exhibited a high ability to transform mouse NIH3T3 cells, but we could not detect any activation of Ha‐ras, Ki‐ras, hst, erbB‐2, mos, met or raf in any of the transformed NIH3T3 cells. These results suggest that even though cultured CHE cells can transform spontaneously, without any specific chromosome change, to immortal cells, activation of unknown oncogene(s) in addition to a specific chromosome change may be required for their malignant progression. Our results suggest that trisomy of chromosome 3q is this specific chromosome change.