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 TGF alpha 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.