Expression of the FUS-CHOP fusion protein in primary mesenchymal progenitor cells gives rise to a model of myxoid liposarcoma

Détails

ID Serval
serval:BIB_DF9B5DDB40A5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Expression of the FUS-CHOP fusion protein in primary mesenchymal progenitor cells gives rise to a model of myxoid liposarcoma
Périodique
Cancer Research
Auteur(s)
Riggi  N., Cironi  L., Provero  P., Suva  M. L., Stehle  J. C., Baumer  K., Guillou  L., Stamenkovic  I.
ISSN
0008-5472 (Print)
Statut éditorial
Publié
Date de publication
2006
Volume
66
Numéro
14
Pages
7016-7023
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
A subset of sarcomas is associated with specific chromosomal translocations that give rise to fusion genes believed to participate in transformation and oncogenesis. Identification of the primary cell environment that provides permissiveness for the oncogenic potential of these fusion genes is essential to understand sarcoma pathogenesis. We have recently shown that expression of the EWS-FLI-1 fusion protein in primary mesenchymal progenitor cells (MPCs) suffices to develop Ewing's sarcoma-like tumors in mice. Because most sarcomas bearing unique chromosomal translocations are believed to originate from common progenitor cells, and because MPCs populate most organs, we expressed the sarcoma-associated fusion proteins FUS/TLS-CHOP, EWS-ATF1, and SYT-SSX1 in MPCs and tested the tumorigenic potential of these cells in vivo. Whereas expression of EWS-ATF1 and SYT-SSX1 failed to transform MPCs, FUS-CHOP-expressing cells formed tumors resembling human myxoid liposarcoma. Transcription profile analysis of these tumors revealed induction of transcripts known to be associated with myxoid liposarcoma and novel candidate genes, including PDGFA, whose expression was confirmed in human tumor samples. MPC(FUS-CHOP) and the previously described MPC(EWS-FLI-1) tumors displayed distinct transcription profiles, consistent with the different target gene repertoires of their respective fusion proteins. Unexpectedly, a set of genes implicated in cell survival and adhesion displayed similar behavior in the two tumors, suggesting events that may be common to primary MPC transformation. Taken together, our observations suggest that expression of FUS-CHOP may be the initiating event in myxoid liposarcoma pathogenesis, and that MPCs may constitute one cell type from which these tumors originate
Mots-clé
Animals/Bone Marrow Cells/metabolism/Pathology/physiology/Cell Transformation,Neoplastic/genetics/Humans/Liposarcoma,Myxoid/Mesenchymal Stem Cells/cytology/Mice/Mice,Inbred C57BL/Mice,Scid/Oncogene Proteins,Fusion/biosynthesis/RNA-Binding Protein FUS/Transcription Factor CHOP/Transfection
Pubmed
Web of science
Création de la notice
29/01/2008 19:35
Dernière modification de la notice
20/08/2019 17:04
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