Synergism between pairs of immortalizing genes in transformation assays of rat embryo fibroblasts.

A number of cellular and viral genes encode proteins that play a role in the establishment of normal cells in culture. In addition, these genes cooperate with activated ras genes to induce cellular transformation. We show that ras-dependent transformation of rat embryo fibroblasts is more efficient when two establishment genes are used together compared with one alone. Both quantitative and qualitative differences in the efficiency of transformation were detected. The number of transformed foci generated was greater than the sum of the foci obtained with ras and each of the establishment genes used separately. In addition, the foci had a distinct morphology. Synergism was seen between the HPV-16 E7 gene and certain mutant alleles of the cellular p53 gene as well as between E7 and c-myc.