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Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice

Oncogene volume 21, pages 1679–1684 (2002)Cite this article

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.

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Acknowledgements

We are grateful to JC Villoria-Terrón for excellent technical assistance with mice. We are indebted to members of lab 13 for helpful discussions, and specific thanks to Prof R González-Sarmiento for his unconditional help and support. This work has been supported by DGCYT (1FD97-0360, SAF2000-0148, BIO2000-0453-P4-02 and 1FD97-1126), Fundación Científica of the AECC, Junta de Castilla y León (C.S.12/99 and C.S.I. 3/01), FIS (99/0935 and 01/0114), and NIH grant (1 R01 CA79955-01). PA Pérez-Mancera and MA Rodríguez-García are scholarship holders from MEC and CSIC-GLAXO, respectively.

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Author notes

  1. Pedro Antonio Pérez-Mancera, Jesus Pérez-Losada and Manuel Sánchez-Martín: PA Pérez-Mancera, J Pérez-Losada and M Sánchez-Martín have made equal contributions to this work

Authors and Affiliations

  1. Instituto de Biologia Molecular y Celular del Cancer (IBMCC), Centro de Investigacion del Cancer, CSIC/Universidad de Salamanca, Campus Unamuno 37007-Salamanca, Spain

    Pedro Antonio Pérez-Mancera, Jesus Pérez-Losada, Manuel Sánchez-Martín, Maria Aranzazu Rodríguez-García & Isidro Sánchez-García

  2. Servicio de Anatomía Patológica, Universidad de Salamanca, Campus Unamuno 37007-Salamanca, Spain

    Teresa Flores

  3. Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Campus Unamuno 37007-Salamanca, Spain

    Enrique Battaner

  4. Area de Reproducción Animal, Centro de Investigación y Tecnología, Ctra de la Coruña km 5.9, 28040, Madrid, Spain

    Alfonso Gutiérrez-Adán & Belen Pintado

Authors
  1. Pedro Antonio Pérez-Mancera
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  2. Jesus Pérez-Losada
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  3. Manuel Sánchez-Martín
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  4. Maria Aranzazu Rodríguez-García
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  5. Teresa Flores
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  6. Enrique Battaner
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  7. Alfonso Gutiérrez-Adán
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  8. Belen Pintado
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  9. Isidro Sánchez-García
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Corresponding author

Correspondence to Isidro Sánchez-García.

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Pérez-Mancera, P., Pérez-Losada, J., Sánchez-Martín, M. et al. Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice. Oncogene 21, 1679–1684 (2002). https://doi.org/10.1038/sj.onc.1205220

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