title: Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice.
abstract: Fusion proteins created by chromosomal abnormalities are key components of mesenchymal cancer development. The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS-CHOP fusion gene. In the past, we generated FUS-CHOP and CHOP transgenic mice and have shown that while FUS-CHOP transgenic develop liposarcomas, mice expressing CHOP, which lacks the FUS domain, display essentially normal white adipose tissue (WAT) development, suggesting that the FUS domain of FUS-CHOP plays a specific and critical role in the pathogenesis of liposarcoma. To test the significance of FUS and CHOP domain interactions within a living mouse, we generated mice expressing the FUS domain and crossed them with CHOP-transgenic mice to generate double-transgenic FUSxCHOP animals. Here we report that expression of the FUS domain restores liposarcoma development in CHOP-transgenic mice. Our results provide genetic evidence that FUS and CHOP domains function in trans for the mutual restoration of liposarcoma. These results identify a new mechanism of tumor-associated fusion genes and might have impact beyond myxoid liposarcoma.
authors.affiliation: Instituto de Biologia Molecular y Celular del Cancer, Centro de Investigacion del Cancer, CSIC/Universidad de Salamanca, Campus Unamuno 37007-Salamanca, Spain.
authors.forename: Pedro Antonio
authors.initials: PA
authors.lastname: Pérez-Mancera
authors.forename: Jesus
authors.initials: J
authors.lastname: Pérez-Losada
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Martín
authors.forename: Maria Aranzazu
authors.initials: MA
authors.lastname: Rodríguez-García
authors.forename: Teresa
authors.initials: T
authors.lastname: Flores
authors.forename: Enrique
authors.initials: E
authors.lastname: Battaner
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gutiérrez-Adán
authors.forename: Belen
authors.initials: B
authors.lastname: Pintado
authors.forename: Isidro
authors.initials: I
authors.lastname: Sánchez-García
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D002454:Cell Differentiation; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008080:Liposarcoma / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins / Q000502:physiology*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; C497250:Ddit3 protein, mouse; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; C106030:TLS-CHOP fusion protein, human; D014157:Transcription Factors; D051742:Transcription Factor CHOP