JUN oncogene amplification and overexpression block adipocytic differentiation in highly aggressive sarcomas.
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.
Mariani
Odette
O
Institut Curie, Genetics and Biology of Cancers, 26 rue d'Ulm, 75248 Paris cedex 05, France; INSERM U830, F-75005 Paris, France.
Brennetot
Caroline
C
Coindre
Jean-Michel
JM
Gruel
Nadège
N
Ganem
Carine
C
Delattre
Olivier
O
Stern
Marc-Henri
MH
Aurias
Alain
A
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
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger