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| Status |
Public on Mar 01, 2016 |
| Title |
EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development [gene expression] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
EWS-FLI1, a multi-functional fusion oncogene, is exclusively detectable in Ewing sarcomas. However, previous studies reported that a subset of osteosarcomas also harbor EWS-ETS family fusion, suggesting that the fusion gene may be involved in the development of a particular type of osteosarcomas. Here using the doxycycline inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also showed that the sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited the impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrated that EWS-FLI1 contributed to in vitro sarcoma development from the sarcoma-iPSCs after osteogenic differentiation. These findings demonstrated that modulating cellular differentiation is fundamental principle of the EWS-FLI1-induced osteosarcoma development. Furthermore, the in vitro cancer model using sarcoma-iPSCs should provide a novel platform for dissecting relationship between cancer genome and cellular differentiation.
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| Overall design |
Microarray in mouse EWS-FLI1-induced osteosarcoma cell lines(SCOS#2 and SCOS#12) and sarcoma(SCOS#2)-derived iPSCs. Total 6 samples were analyzed. We can induce EWS-FLI1 expression by Doxycycline-inducible expression system in SCOS#2 and #12. We investigaed EWS-FLI1 activated genes (Dox ON-High) and EWS-FLI1 repressed genes (Dox OFF-High) in SCOS#2 and #12 sarcoma cell lines. Also, we investigated global gene expression pattern of sarcoma-derived iPSCs (iPSC#2-A1 and #2-B5). A link to this sample file can be found below.
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| Contributor(s) |
Komura S, Itakura F, Yamada Y |
| Citation(s) |
26997645 |
| |
| Submission date |
Sep 03, 2015 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Yasuhiro Yamada |
| E-mail(s) |
yyamada@m.u-tokyo.ac.jp
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| Organization name |
University of Tokyo
|
| Department |
Department of Molecular Pathology
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| Street address |
7-3-1 Hongo, Bunkyo-ku
|
| City |
Tokyo |
| ZIP/Postal code |
113-0033 |
| Country |
Japan |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE72898 |
EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development |
|
| Relations |
| BioProject |
PRJNA294699 |
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