Suppression of Ras-stimulated transformation by the JNK signal transduction pathway
Howard Hughes Medical Institute; Program in Molecular Medicine; Department of Cancer Biology; Department of Cell Biology
Animals; Cell Line; Cell Transformation, Neoplastic; Fibroblasts; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Nude; Mitogen-Activated Protein Kinases; Neoplasms, Experimental; Signal Transduction; ras Proteins
Life Sciences | Medicine and Health Sciences
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.
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Citation: Genes Dev. 2003 Mar 1;17(5):629-37. Link to article on publisher's site