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Title

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

AuthorsPérez-Losada, J. ; Sánchez García, Isidro
Issue Date2000
PublisherNature Publishing Group
CitationOncogene 19(20): 2413-2422 (2000)
AbstractThe 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 1 (EF1) 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 PPAR, 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 PPAR expression. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1 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.
URIhttp://hdl.handle.net/10261/6282
ISSN0950-9232
Appears in Collections:(IMB) Artículos
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