Tumor induction by activated JNK occurs through deregulation of cellular growth.
Activation of the cytoplasmic (Ras-Raf-MEK-ERK) signaling cascade was shown to be both, necessary and sufficient for transformation in vitro as well as in vivo. However, over the last years the involvement of stress-activated protein kinases (SAPKs)/Jun N-terminal kinases (JNKs), and their substrate c-Jun in the process of cellular transformation has been suggested. To dissect the mechanisms through which JNK signaling contributes to the transformation process we employed a recently generated constitutively active version of this kinase, SAPKbeta-MKK7, which behaves like a weakly transforming oncogene in vitro. Dissection of the transforming potential of oncogenic JNK demonstrates that it is sufficient for tumor induction in nude mice. In vitro studies and analysis of tumor material support the conclusion that oncogenic JNK primarily transforms through its effects on cell proliferation and tumor vascularization but does not affect cell survival.
Rennefahrt
Ulrike
U
Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Würzburg, Germany.
Illert
Bertram
B
Greiner
Axel
A
Rapp
Ulf R
UR
Troppmair
Jakob
J
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism
D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482566:MAP2K6 protein, human; C482567:Map2k6 protein, mouse