EVIDENCE FOR CELL-SPECIFIC DIFFERENCES IN TRANSFORMATION BY N-RAS, H-RAS AND K-RAS

Although Ras plays a fundamental role in cellular proliferation, diffe rentiation and transformation, clear functional differences between th e three major Ras proteins (N-, H- and K-Ras) have not as yet been dem onstrated. In this study, chimeric constructs were used to compare dir ectly transformation by N-, H- and E-vas oncogenes. In Rat-2 and MH3T3 fibroblasts, transformation assays (anchorage independence, focus-for mation and growth in 1% FCS) showed that H-12-Ras was more transformin g than N-12-Ras or K-12-Ras. By contrast, in the human multipotent hae mopoietic cell line, TF-1, N-12-Ras exhibited greater biological activ ity. Northern blotting and protein analyses indicated that these findi ngs were not the result of differences in expression or stability of p 21Ras. Using further H-ras/N-ras chimeric constructs, we found that th e greater transforming activity of H-12-Ras in fibroblasts was not due to the hypervariable-CAAX region, but rather to unique sequences betw een amino acids 84 and 143. These data demonstrate cell specific diffe rences in the intrinsic transforming potential of N-ras, H-ras and K-r as oncogenes.