Rapid induction of an experimental metastatic phenotype in first passage rat embryo cells by cotransfection of EJ c-Ha-ras and c-myc oncogenes.

First passage rat embryo cells were transfected with plasmids carrying a mutated EJ c-Ha-ras oncogene alone or in combination with the c-myc oncogene. Three days later, unselected cultures were harvested and injected into nude mice either subcutaneously to assay for tumorigenicity or intravenously to assay for metastasis to the lung. The results indicate that a transcriptionally-enhanced EJ-c-Ha-ras oncogene alone can convert normal rat cells to a tumorigenic but not metastatic phenotype. Co-transfection of a c-myc oncogene with the EJ c-Ha-ras oncogene was necessary to produce the rapid, phenotypic conversion of normal cells to transformed cells with both tumorigenic and metastatic potential. No tumors were observed in animals injected with c-myc-transfected cells. Cell lines established from EJ c-Ha-ras-induced shoulder tumors were metastatic when reinjected intravenously into nude mice. These results support the hypothesis that the cooperative action of c-Ha-ras and c-myc oncogenes is more potent in inducing malignant transformation than either oncogene acting alone. Our results also suggest that the phenotypic conversion of normal cells to tumorigenic cells with experimental metastatic potential by ras and myc oncogenes can be completed within 3-4 cell divisions after transfection.