The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice
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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Format: | artículo biblioteca |
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Springer Nature
2000
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Subjects: | Chromosomal abnormality, Malignant solid tumors, Adipose tissue, Cancer development, |
Online Access: | http://hdl.handle.net/20.500.12792/3460 http://hdl.handle.net/10261/289748 |
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dig-inia-es-10261-2897482023-02-16T12:23:48Z The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice Pérez-Losada, J. Pintado, B. Gutiérrez Adán, Alfonso Flores, T. Bañares-González, B. Calabia del Campo, J. Martín-Martín, J. F. Battaner, E. Sánchez-García, I. Chromosomal abnormality Malignant solid tumors Adipose tissue Cancer development 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. 2023-02-16T12:23:48Z 2023-02-16T12:23:48Z 2000 artículo Oncogene 19(20): 2413-2422 (2000) 0950-9232 http://hdl.handle.net/20.500.12792/3460 http://hdl.handle.net/10261/289748 10.1038/sj.onc.1203572 1476-5594 en none Springer Nature |
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Chromosomal abnormality Malignant solid tumors Adipose tissue Cancer development Chromosomal abnormality Malignant solid tumors Adipose tissue Cancer development |
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Chromosomal abnormality Malignant solid tumors Adipose tissue Cancer development Chromosomal abnormality Malignant solid tumors Adipose tissue Cancer development Pérez-Losada, J. Pintado, B. Gutiérrez Adán, Alfonso Flores, T. Bañares-González, B. Calabia del Campo, J. Martín-Martín, J. F. Battaner, E. Sánchez-García, I. The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice |
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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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artículo |
topic_facet |
Chromosomal abnormality Malignant solid tumors Adipose tissue Cancer development |
author |
Pérez-Losada, J. Pintado, B. Gutiérrez Adán, Alfonso Flores, T. Bañares-González, B. Calabia del Campo, J. Martín-Martín, J. F. Battaner, E. Sánchez-García, I. |
author_facet |
Pérez-Losada, J. Pintado, B. Gutiérrez Adán, Alfonso Flores, T. Bañares-González, B. Calabia del Campo, J. Martín-Martín, J. F. Battaner, E. Sánchez-García, I. |
author_sort |
Pérez-Losada, J. |
title |
The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice |
title_short |
The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice |
title_full |
The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice |
title_fullStr |
The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice |
title_full_unstemmed |
The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice |
title_sort |
chimeric fus/tls-chop fusion protein specifically induces liposarcomas in transgenic mice |
publisher |
Springer Nature |
publishDate |
2000 |
url |
http://hdl.handle.net/20.500.12792/3460 http://hdl.handle.net/10261/289748 |
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