Ha-Ras-1 oncogene dosage differentially affects Balb/3T3 cells' growth factor requirement and tumorigenicity

The effect of EJ-ras oncogene dosage on the phenotype of Balb/3T3 transfectants was analyzed with respect to: a) peptide growth factors' requirement; b) relaxation of cell cycle control; c) tumorigenic potential. Mouse embryo-derived Balb/3T3 cells were transfected with the mutated form of the human c-Ha-ras-1 (EJ-ras) along with a genetic marker (neo gene). Transfectants displaying high EJ-ras expression presented a relaxed cell cycle control, required only insulin to initiate DNA synthesis and were highly tumorigenic. On the other hand, low expression EJ-ras transfectants required both competence (FGF) and progression factors (EGF and insulin) exactly like the parental cells. But, upon serial cultivation, these transfectants became fully transformed and highly tumorigenic without EJ-ras amplification and/or overexpression. Therefore, low EJ-ras expression primes the cells to become tumorigenic but neither overrides the cells' requirement for competence growth factor nor deregulates the cell cycle.