The N-ras proto-oncogene can suppress the malignant phenotype in the presence or absence of its oncogene

ras proto-oncogenes have traditionally been associated with the regulation and promotion of cell growth. We have induced thymic lymphomas in N-ras-/- mice and in transgenic mice that overexpress wild-type N-ras and found that the lack of wild-type N-ras alleles favors the development of thymic lymphomas, whereas overexpression of wild-type N-ras protects against thymic lymphomagenesis in the presence or absence of its oncogene. To investigate the inhibitory role of wild-type N-ras in in vitro transformation, we introduced wild-type N-ras in N-ras-deficient tumor cells that lack ras activating mutations and found decreased growth in both low serum and soft agar. Taken together, our results indicate that wild-type N-ras has "tumor suppressor" activity, even in the absence of its oncogenic allele.