title: JUN oncogene amplification and overexpression block adipocytic differentiation in highly aggressive sarcomas.
abstract: The human oncogene JUN encodes a component of the AP-1 complex and is consequently involved in a wide range of pivotal cellular processes, including cell proliferation, transformation, and apoptosis. Nevertheless, despite extensive analyses of its functions, it has never been directly involved in a human cancer. We demonstrate here that it is highly amplified and overexpressed in undifferentiated and aggressive human sarcomas, which are blocked at an early step of adipocyte differentiation. We confirm by cellular and xenograft mouse models recapitulating these sarcoma genetics that the failure to differentiate is dependent upon JUN amplification/overexpression.
authors.affiliation: Institut Curie, Genetics and Biology of Cancers, 26 rue d'Ulm, 75248 Paris cedex 05, France; INSERM U830, F-75005 Paris, France.
authors.forename: Odette
authors.initials: O
authors.lastname: Mariani
authors.forename: Caroline
authors.initials: C
authors.lastname: Brennetot
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
authors.forename: Nadège
authors.initials: N
authors.lastname: Gruel
authors.forename: Carine
authors.initials: C
authors.lastname: Ganem
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Marc-Henri
authors.initials: MH
authors.lastname: Stern
authors.forename: Alain
authors.initials: A
authors.lastname: Aurias
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology*; D050156:Adipogenesis; D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D022202:Chromosomes, Artificial, Bacterial; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012186:Retroperitoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger