title: Rap1-suppressed tumorigenesis is concomitant with the interference in ras effector signaling.
abstract: Expression of Rap1 blocks epithelial growth factor-induced extracellular signal-regulated kinases (ERKs) activation. However, recent studies demonstrated that Rap1 mediates ERKs activation induced by nerve growth factor. The anti-oncogenic effect of Rap1 has been reported but its mechanism remains unclear. To evaluate the correlation between the anti-transforming effect and the activation of ERKs, we transfected rap1 cDNA into Hep3B cells and selected stable transfectants. The Rap1 transfectants completely lost their intrinsic tumorigenicity in Balb/c nude mice. Both insulin and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated ERK activations were also blocked. Our findings suggest that Rap1-suppressed tumorigenicity is concomitant with ERKs inhibition.
authors.affiliation: Institut de Génétique Humaine, Centre National de la Recherche Scientifique, 141 rue de la Cardonille, 34396, Montpellier, France. ylin@igh.cnrs.fr
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Mettling
authors.forename: C
authors.initials: C
authors.lastname: Chou
mesh_terms: D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D007328:Insulin; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020932:Nerve Growth Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D014162:Transfection; D014407:Tumor Cells, Cultured; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases; D020827:rap1 GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate