ONCOGENE TRANSFORMATION FREQUENCY OF NONSENESCENT SFME CELLS IS INCREASED BY C-MYC

Immortalized, postcrisis mouse embryo cell cultures derived in serum-containing medium display genomic abnormalities and an altered, preneoplastic phenotype. These lines can be transformed with single oncogenes, such as Ha-ras, while efficient transformation of precrisis, genomically unaltered rodent embryo cultures require cooperating oncogenes, such as Ha-ras and the mouse c-myc gene constitutively expressed. Serum-free mouse embryo (SFME) cells, cultured under conditions in which serum is replaced by growth factors and other supplements, are 'immortalized' in the genomically unaltered state. SFME cells do not exhibit growth crisis or gross chromosomal aberration, and are dependent on epidermal growth factor for survival, growth inhibited by serum, and are nontumorigenic. Transformation of SFME cells can be achieved with ras alone, but the introduction of c-myc increased the transfection frequency upon subsequent transfection with ras by as much as twenty fold. Similar results were obtained with mutationally activated neu oncogene and with genomic human tumor DNA. Constitutive expression of c-myc alone did not alter the properties of the SFME cells. These results demonstrate that c-myc alters cellular responses to oncogenes in a culture system in which oncogene-induced immortalization is not a factor, indicating that the effects of myc may extend beyond an 'immortalization' function in these cells.