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  • Original Paper
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The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice

Oncogene volume 19, pages 2413–2422 (2000)Cite this article

Abstract

The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that encodes the FUS-CHOP chimeric protein, is associated with human liposarcomas. The altered expression of FUS-CHOP has been implicated in a characteristic subgroup of human liposarcomas. We have introduced the FUS-CHOP transgene into the mouse genome in which the expression of the transgene is successfully driven by the elongation factor 1α (EF1α) promoter to all tissues. The consequent overexpression of FUS-CHOP results in most of the symptoms of human liposarcomas, including the presence of lipoblasts with round nuclei, accumulation of intracellular lipid, induction of adipocyte-specific genes and a concordant block in the differentiation program. We have demonstrated that liposarcomas in the FUS-CHOP transgenic mice express high levels of the adipocyte regulatory protein PPARγ, whereas it is not expressed in embryonic fibroblasts from these animals following induction to differentiation toward the adipocyte lineage, indicating that the in vitro system does not really reflect the in vivo situation and the developmental defect is downstream of PPARγ expression. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1α promoter. This establishes FUS-CHOP overexpression as a key determinant of human liposarcomas and provide the first in vivo evidence for a link between a fusion gene created by a chromosomal translocation and a solid tumor.

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Acknowledgements

We are grateful to Dr R Arévalo for providing the histological facilities. We are indebted to Dr C Cobaleda for help in the preparation of the manuscript, and specific thanks to JC Villoria-Terrón and JF Martín-Martín for excellent technical advice. This work has been supported by European Commission (BMH4-CT96-0375), DGCYT (UE96-0041, PB96-0816 and 1FD97-0360), Fundación Científica of the AECC, FIS (99/0935) and NIH grant (1 R01 CA79955-01).

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Authors and Affiliations

  1. Departamento de Proliferación y Diferenciacion Celular, Instituto de Microbiología Bioquímica, CSIC/Universidad de Salamanca, Edificio Departamental, Avda del Campo Charro s/n, Salamanca, 37007, Spain

    J Pérez-Losada, J F Martín-Martín & I Sánchez-García

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

    B Pintado & A Gutiérrez-Adán

  3. Servicio de Anatomía Patológica, Universidad de Salamanca, Spain

    T Flores

  4. Servicio de Radiodiagnóstico, Universidad de Salamanca, Spain

    B Bañares-González & J Calabia del Campo

  5. Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Spain

    E Battaner

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  1. J Pérez-Losada
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  2. B Pintado
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Pérez-Losada, J., Pintado, B., Gutiérrez-Adán, A. et al. The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice. Oncogene 19, 2413–2422 (2000). https://doi.org/10.1038/sj.onc.1203572

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