Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice.
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.
Pérez-Mancera
Pedro Antonio
PA
Instituto de Biologia Molecular y Celular del Cancer, Centro de Investigacion del Cancer, CSIC/Universidad de Salamanca, Campus Unamuno 37007-Salamanca, Spain.
Pérez-Losada
Jesus
J
Sánchez-Martín
Manuel
M
Rodríguez-García
Maria Aranzazu
MA
Flores
Teresa
T
Battaner
Enrique
E
Gutiérrez-Adán
Alfonso
A
Pintado
Belen
B
Sánchez-García
Isidro
I
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*
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