IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells
| Autor: | Nicolo Riggi, Luisa Cironi, Domizio Suva, Paolo Provero, Natalie Wolf, Mario-Luca Suvà, Vincent Kindler, Ivan Stamenkovic |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Oncogene Proteins
Oncogene Proteins Fusion Animals Gene Expression Profiling Gene Expression Regulation Humans Insulin-Like Growth Factor I/metabolism Mesenchymal Stromal Cells/cytology Mesenchymal Stromal Cells/metabolism Mice Mice Inbred C57BL Models Biological Oncogene Proteins Fusion/chemistry Oncogene Proteins Fusion/metabolism Phenotype Promoter Regions Genetic Proto-Oncogene Protein c-fli-1/chemistry Proto-Oncogene Protein c-fli-1/metabolism RNA-Binding Protein EWS RNA-Binding Protein FUS/metabolism Transcription Factors/metabolism Oncology/Sarcomas lcsh:Medicine Chimeric gene Biology 03 medical and health sciences 0302 clinical medicine Progenitor cell Insulin-Like Growth Factor I lcsh:Science 030304 developmental biology Regulation of gene expression 0303 health sciences Multidisciplinary Cell fusion Proto-Oncogene Protein c-fli-1 ETS transcription factor family lcsh:R Mesenchymal Stem Cells Fusion protein Pathology/Molecular Pathology 030220 oncology & carcinogenesis Cancer research RNA-Binding Protein FUS Oncology/Pediatric Oncology lcsh:Q Ewing sarcoma Research Article Transcription Factors |
| Zdroj: | PLoS ONE, Vol 3, Iss 7, p e2634 (2008) PLoS ONE PloS one, vol. 3, no. 7, pp. e2634 |
| ISSN: | 1932-6203 |
| Popis: | 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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. |
| Databáze: | OpenAIRE |
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