[Rhabdomyosarcoma development in Trp53/fos mutant mice: tumor suppressor functions of the Fos protooncogene].
Rhabdomyosarcoma is the most common soft tissue sarcoma in children, yet the genetic changes causing this disease are poorly understood. The Fos protein, a major component of the AP-1 transcription factor, is essential for osteoclast differentiation, acts as an oncogene, potentiates transforming signals and controls invasive growth and angiogenesis during tumor progression. To genetically investigate a potential interaction between the p53 and Fos pathways, Trp53/Fos double knock-out mice were generated. These mice develop highly proliferative and invasive rhabdomyosarcomas of the facial and orbital regions with more than 90% penetrance at 6 months of age. Expression of Fos in Trp53/Fos mutant rhabdomyosarcoma cell lines established from primary tumors is associated with enhanced apoptosis and downregulation of Pax7 expression. Our results show that Trp53/Fos double knock-out mice recapitulate major aspects of human rhabdomyosarcoma development and therefore provide a mouse model for the human disease. Furthermore, this study identifies a novel and unexpected tumor suppressive function of the Fos proto-oncogene.
Jochum
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Institut für Klinische Pathologie, Departement Patholgie, Universitätsspital Zürich, Schweiz.
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D017353:Gene Deletion; D016762:Genes, fos; D016158:Genes, p53; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009154:Mutation; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos