CELLULAR RAS GENE ACTIVITY IS REQUIRED FOR FULL NEOPLASTIC TRANSFORMATION BY THE LARGE TUMOR-ANTIGEN OF SV40

To investigate the role of the cellular ras gene product in neoplastic transformation by the SV40 large tumor antigen (SVLT), murine C3H10T1 /2 cells were rendered deficient in Ras activity by transfection with inducible or constitutive antisense ras gene constructs or through the introduction of the dominant-negative mutant, ras(asn17). Consistent with previous results, SVLT-induced morphological transformation was u naffected by the down-regulation of c-ras gene product activity, On th e other hand, colony formation in soft agar and tumorigenicity in nude mice were drastically reduced in c-Ras-deficient cells. In addition, SVLT expression in C3H10T1/2 cells led to increased c-Ras activity, as determined by an increase in the Ras-bound GTP/GTP + GDP ratio, These results suggest that c-Ras is required for full neoplastic transforma tion by SVLT.