Human Gene Set: MIYAGAWA_TARGETS_OF_EWSR1_ETS_FUSIONS_DN


Standard name MIYAGAWA_TARGETS_OF_EWSR1_ETS_FUSIONS_DN
Systematic name M2256
Brief description Genes commonly down-regulated in UET-13 cells (mesenchymal progenitor) by expression of EWSR1 [GeneID=2130] fusions with ETS transcription factors FLI1 and ERG [GeneID=2313] [GeneID=2078].
Full description or abstract Ewing's family tumor (EFT) is a rare pediatric tumor of unclear origin that occurs in bone and soft tissue. Specific chromosomal translocations found in EFT cause EWS to fuse to a subset of ets transcription factor genes (ETS), generating chimeric EWS/ETS proteins. These proteins are believed to play a crucial role in the onset and progression of EFT. However, the mechanisms responsible for the EWS/ETS-mediated onset remain unclear. Here we report the establishment of a tetracycline-controlled EWS/ETS-inducible system in human bone marrow-derived mesenchymal progenitor cells (MPCs). Ectopic expression of both EWS/FLI1 and EWS/ERG proteins resulted in a dramatic change of morphology, i.e., from a mesenchymal spindle shape to a small round-to-polygonal cell, one of the characteristics of EFT. EWS/ETS also induced immunophenotypic changes in MPCs, including the disappearance of the mesenchyme-positive markers CD10 and CD13 and the up-regulation of the EFT-positive markers CD54, CD99, CD117, and CD271. Furthermore, a prominent shift from the gene expression profile of MPCs to that of EFT was observed in the presence of EWS/ETS. Together with the observation that EWS/ETS enhances the ability of cells to invade Matrigel, these results suggest that EWS/ETS proteins contribute to alterations of cellular features and confer an EFT-like phenotype to human MPCs.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18212050   Authors: Miyagawa Y,Okita H,Nakaijima H,Horiuchi Y,Sato B,Taguchi T,Toyoda M,Katagiri YU,Fujimoto J,Hata J,Umezawa A,Kiyokawa N
Exact source Table 2S
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.1: First introduced


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