title: Inhibition of Ras oncogenic activity by Ras protooncogenes.
abstract: Point mutations in ras genes have been found in a large number and wide variety of human tumors. These oncogenic Ras mutants are locked in an active GTP-bound state that leads to a constitutive and deregulated activation of Ras function. The dogma that ras oncogenes are dominant, whereby the mutation of a single allele in a cell will predispose the host cell to transformation regardless of the presence of the normal allele, is being challenged. We have seen that increasing amounts of Ras protooncogenes are able to inhibit the activity of the N-Ras oncogene in the activation of Elk in NIH 3T3 cells and in the formation of foci. We have been able to determine that the inhibitory effect is by competition between Ras protooncogenes and the N-Ras oncogene that occurs first at the effector level at the membranes, then at the processing level and lastly at the effector level in the cytosol. In addition, coexpression of the N-Ras protooncogene in thymic lymphomas induced by the N-Ras oncogene is associated with increased levels of p107, p130 and cyclin A and decreased levels of Rb. In the present report, we have shown that the N-Ras oncogene is not truly dominant over Ras protooncogenes and their competing activities might be depending on cellular context.
authors.affiliation: Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Diaz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lue
authors.forename: Jeremy
authors.initials: J
authors.lastname: Mathews
authors.forename: Andrew
authors.initials: A
authors.lastname: Yoon
authors.forename: Daniel
authors.initials: D
authors.lastname: Ahn
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-España
authors.forename: Peter
authors.initials: P
authors.lastname: Leonardi
authors.forename: Marcelo P
authors.initials: MP
authors.lastname: Vargas
authors.forename: Angel
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D002471:Cell Transformation, Neoplastic; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008223:Lymphoma / Q000473:pathology*; D010641:Phenotype; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary