title: c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma.
abstract: We have investigated the role of individual members of the Raf/Mek/Erk cascade in the onset of K-Ras oncogene-driven non-small cell lung carcinoma (NSCLC). Ablation of Erk1 or Erk2 in K-Ras oncogene-expressing lung cells had no significant effect due to compensatory activities. Yet, elimination of both Erk kinases completely blocked tumor development. Similar results were obtained with Mek kinases. Ablation of B-Raf had no significant effect on tumor development. However, c-Raf expression was absolutely essential for the onset of NSCLC. Interestingly, concomitant elimination of c-Raf and B-Raf in adult mice had no deleterious consequences for normal homeostasis. These results indicate that c-Raf plays a unique role in mediating K-Ras signaling and makes it a suitable target for therapeutic intervention.
authors.affiliation: Molecular Oncology, Centro Nacional de Investigaciones Oncológicas (CNIO), E-28029 Madrid, Spain.
authors.forename: Rafael B
authors.initials: RB
authors.lastname: Blasco
authors.forename: Sarah
authors.initials: S
authors.lastname: Francoz
authors.forename: David
authors.initials: D
authors.lastname: Santamaría
authors.forename: Marta
authors.initials: M
authors.lastname: Cañamero
authors.forename: Pierre
authors.initials: P
authors.lastname: Dubus
authors.forename: Jean
authors.initials: J
authors.lastname: Charron
authors.forename: Manuela
authors.initials: M
authors.lastname: Baccarini
authors.forename: Mariano
authors.initials: M
authors.lastname: Barbacid
mesh_terms: D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D048369:MAP Kinase Kinase 1 / Q000172:deficiency / Q000235:genetics; D048370:MAP Kinase Kinase 2 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000172:deficiency / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000172:deficiency / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: C482119:BRAF protein, human; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482127:Map2k1 protein, mouse; C482129:Map2k2 protein, mouse