Expression of the FUS-CHOP Fusion Protein in Primary Mesenchymal Progenitor Cells Gives Rise to a Model of Myxoid Liposarcoma
- 15 July 2006
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 66 (14), 7016-7023
- https://doi.org/10.1158/0008-5472.can-05-3979
Abstract
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.Keywords
Other Versions
This publication has 39 references indexed in Scilit:
- Understanding mesenchymal cancer: the liposarcoma-associated FUS–DDIT3 fusion gene as a modelSeminars in Cancer Biology, 2005
- Comparable transforming capacities and differential gene expression patterns of variant FUS/CHOP fusion transcripts derived from soft tissue liposarcomasOncogene, 2004
- Mesenchymal stem cells: clinical applications and biological characterizationThe International Journal of Biochemistry & Cell Biology, 2004
- Temperature-Dependent Localization of TLS?CHOP to Splicing Factor CompartmentsExperimental Cell Research, 2002
- Pluripotency of mesenchymal stem cells derived from adult marrowNature, 2002
- Cytokine serum levels in soft tissue sarcoma patients: Correlations with clinico‐pathological features and prognosisInternational Journal of Cancer, 2002
- Expression of the FUS domain restores liposarcoma development in CHOP transgenic miceOncogene, 2002
- Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformationOncogene, 2001
- RGS2 Promotes Adipocyte Differentiation in the Presence of Ligand for Peroxisome Proliferator-activated Receptor γPublished by Elsevier BV ,2001
- Overexpression of the Hepatocyte Growth Factor (HGF) Receptor (Met) and Presence of a Truncated and Activated Intracellular HGF Receptor Fragment in Locally Aggressive/Malignant Human Musculoskeletal TumorsThe American Journal of Pathology, 2000