title: IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells.
abstract: BACKGROUND
  The EWS-FLI-1 fusion protein is associated with 85-90% of Ewing's sarcoma family tumors (ESFT), the remaining 10-15% of cases expressing chimeric genes encoding EWS or FUS fused to one of several ets transcription factor family members, including ERG-1, FEV, ETV1 and ETV6. ESFT are dependent on insulin-like growth factor-1 (IGF-1) for growth and survival and recent evidence suggests that mesenchymal progenitor/stem cells constitute a candidate ESFT origin.
  
  
  RESULTS
  To address the functional relatedness between ESFT-associated fusion proteins, we compared mouse progenitor cell (MPC) permissiveness for EWS-FLI-1, EWS-ERG and FUS-ERG expression and assessed the corresponding expression profile changes. Whereas all MPC isolates tested could stably express EWS-FLI-1, only some sustained stable EWS-ERG expression and none could express FUS-ERG for more than 3-5 days. Only 14% and 4% of the total number of genes that were respectively induced and repressed in MPCs by the three fusion proteins were shared. However, all three fusion proteins, but neither FLI-1 nor ERG-1 alone, activated the IGF1 promoter and induced IGF1 expression.
  
  
  CONCLUSIONS
  Whereas expression of different ESFT-associated fusion proteins may require distinct cellular microenvironments and induce transcriptome changes of limited similarity, IGF1 induction may provide one common mechanism for their implication in ESFT pathogenesis.
authors.affiliation: Division of Experimental Pathology, Institute of Pathology CHUV, University of Lausanne, Lausanne, Switzerland.
authors.forename: Luisa
authors.initials: L
authors.lastname: Cironi
authors.forename: Nicolò
authors.initials: N
authors.lastname: Riggi
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
authors.forename: Natalie
authors.initials: N
authors.lastname: Wolf
authors.forename: Mario-Luca
authors.initials: ML
authors.lastname: Suvà
authors.forename: Domizio
authors.initials: D
authors.lastname: Suvà
authors.forename: Vincent
authors.initials: V
authors.lastname: Kindler
authors.forename: Ivan
authors.initials: I
authors.lastname: Stamenkovic
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D015514:Oncogene Proteins, Fusion / Q000737:chemistry* / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051789:Proto-Oncogene Protein c-fli-1 / Q000737:chemistry* / Q000378:metabolism; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C450460:EWS-ERG fusion protein, human; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; C107302:TLS-ERG fusion protein, human; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I