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Titolo:
The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomasin transgenic mice
Autore:
Perez-Losada, J; Pintado, B; Gutierrez-Adan, A; Flores, T; Banares-Gonzalez, B; del Campo, JC; Martin-Martin, JF; Battaner, E; Sanchez-Garcia, I;
Indirizzi:
Univ Salamanca, CSIC, Inst Microbiol Bioquim, Dept Proliferac & Diferenciac Celular, Salamanca 37007, Spain Univ Salamanca Salamanca Spain 37007 iac Celular, Salamanca 37007, Spain Ctr Invest & Tecnol, Area Reprod Anim, Madrid 28040, Spain Ctr Invest & Tecnol Madrid Spain 28040 Reprod Anim, Madrid 28040, Spain Univ Salamanca, Serv Anat Patol, E-37008 Salamanca, Spain Univ Salamanca Salamanca Spain E-37008 t Patol, E-37008 Salamanca, Spain Univ Salamanca, Serv Radiodiagnost, E-37008 Salamanca, Spain Univ Salamanca Salamanca Spain E-37008 iagnost, E-37008 Salamanca, Spain Univ Salamanca, Dept Bioquim & Biol Mol, E-37008 Salamanca, Spain Univ Salamanca Salamanca Spain E-37008 iol Mol, E-37008 Salamanca, Spain
Titolo Testata:
ONCOGENE
fascicolo: 20, volume: 19, anno: 2000,
pagine: 2413 - 2422
SICI:
0950-9232(20000511)19:20<2413:TCFFPS>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENHANCER-BINDING-PROTEIN; HUMAN MYELOID-LEUKEMIA; ADIPOCYTE DIFFERENTIATION; CHROMOSOMAL TRANSLOCATION; MYXOID LIPOSARCOMA; TRANSCRIPTIONAL ACTIVATION; ONCOGENIC TRANSFORMATION; RETINOIC ACID; C/EBP-ALPHA; GENE;
Keywords:
chromosomal abnormality; malignant solid tumors; adipose tissue; cancer development;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Sanchez-Garcia, I Univ Salamanca, CSIC, Inst Microbiol Bioquim, Dept Proliferac & Diferenciac Celular, Edificio Dept,Avda Campo Charro S-N, Salamanca37007, Spain Univ Salamanca Edificio Dept,Avda Campo Charro S-N SalamancaSpain 37007
Citazione:
J. Perez-Losada et al., "The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomasin transgenic mice", ONCOGENE, 19(20), 2000, pp. 2413-2422

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 introducedthe FUS-CHOP transgene into the mouse genome in which the expression of the transgene is successfully driven by the elongation factor 1 alpha (EF1 alpha) 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 gamma, 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 gamma expression. No tumors of other tissues were found in these transgenic mice despite widespreadactivity of the EF1 alpha promoter. This establishes FUS-CHOP overexpression as a key determinant of human liposarcomas and provide the first in vivoevidence for a link between a fusion gene created by a chromosomal translocation and a solid tumor.

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Documento generato il 21/09/20 alle ore 06:20:20