title: Requirement of c-Jun NH(2)-terminal kinase for Ras-initiated tumor formation.
abstract: The c-Jun NH(2)-terminal kinase (JNK) signal transduction pathway causes increased gene expression mediated, in part, by members of the activating transcription factor protein (AP1) group. JNK is therefore implicated in the regulation of cell growth and cancer. To test the role of JNK in Ras-induced tumor formation, we examined the effect of compound ablation of the ubiquitously expressed genes Jnk1 plus Jnk2. We report that JNK is required for Ras-induced transformation of p53-deficient primary cells in vitro. Moreover, JNK is required for lung tumor development caused by mutational activation of the endogenous KRas gene in vivo. Together, these data establish that JNK plays a key role in Ras-induced tumorigenesis.
authors.affiliation: Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cellurale
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Sabio
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Kennedy
authors.forename: Madhumita
authors.initials: M
authors.lastname: Das
authors.forename: Marissa
authors.initials: M
authors.lastname: Barlow
authors.forename: Peter
authors.initials: P
authors.lastname: Sandy
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D003260:Contact Inhibition; D005347:Fibroblasts / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D015820:Cadherins; D016159:Tumor Suppressor Protein p53; D048031:JNK Mitogen-Activated Protein Kinases; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)