The Involvement of Activated ras Genes in Determining the Transformed Phenotype

Activated ras oncogenes have been identified in a wide range of tumours. All examples of ras gene activation in tumours so far result from amino acid substitution at Gly¹² or Gln⁶¹. To learn more about how mutations in ras genes lead to transformation, we have analysed transforming growth factor production in NIH/3T3 cells transformed by each of the three ras genes. These results show that the transformed phenotype of these cells results from a combination of the presence of the mutant ras protein and TGFα production. In a second series of experiments we have shown that the mutation of a ras gene in a tumour cell line can lead to tumour progression towards a more aggressive phenotype.