title: The N-ras proto-oncogene can suppress the malignant phenotype in the presence or absence of its oncogene.
abstract: 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.
authors.affiliation: Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Diaz
authors.forename: Daniel
authors.initials: D
authors.lastname: Ahn
authors.forename: Lluis
authors.initials: L
authors.lastname: Lopez-Barcons
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
authors.forename: Ignacio
authors.initials: I
authors.lastname: Perez de Castro
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lue
authors.forename: Neus
authors.initials: N
authors.lastname: Ferrer-Miralles
authors.forename: Ramon
authors.initials: R
authors.lastname: Mangues
authors.forename: Jerry
authors.initials: J
authors.lastname: Tsong
authors.forename: Roberto
authors.initials: R
authors.lastname: Garcia
authors.forename: Roman
authors.initials: R
authors.lastname: Perez-Soler
authors.forename: Angel
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000483:Alleles; D000818:Animals; D003433:Crosses, Genetic; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008223:Lymphoma / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013953:Thymus Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018631:ras Proteins