title: Suppression of Ras-stimulated transformation by the JNK signal transduction pathway.
abstract: The c-Jun NH(2)-terminal kinase (JNK) phosphorylates and activates members of the activator protein-1 (AP-1) group of transcription factors and is implicated in oncogenic transformation. To examine the role of JNK, we investigated the effect of JNK deficiency on Ras-stimulated transformation. We demonstrate that although JNK does play a role in transformation in vitro, JNK is not required for tumor development in vivo. Importantly, the loss of JNK expression resulted in substantial increases in the number and growth of tumor nodules in vivo. Complementation assays demonstrated that this phenotype was caused by JNK deficiency. These data demonstrate that, in contrast to expectations, the normal function of JNK may be to suppress tumor development in vivo. This conclusion is consistent with the presence in human tumors of loss-of-function mutations in the JNK pathway.
authors.affiliation: Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Kennedy
authors.forename: Hayla K
authors.initials: HK
authors.lastname: Sluss
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Jones
authors.forename: Dafna
authors.initials: D
authors.lastname: Bar-Sagi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D051379:Mice; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins