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The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes developmental defects in zebrafish embryos

ABSTRACT: The fusion oncoprotein EWS-FLI1 arises from a t(11;22)(q24;q12) chromosomal translocation and causes Ewing's Sarcoma, a malignant bone tumor. The mechanism whereby EWS-FLI1 transforms cells is unknown. We made germline transgenic zebrafish expressing human EWS-FLI1 under the control of the heat shock promoter. Induction of EWS-FLI1 expression causes multiple defects in embryonic development. We compared gene expression in control and transgenic EWS-FLI1 zebrafish. The results identify a conserved set of EWS-FLI1-regulated genes, and provide insight into the pathogenesis of Ewing's Sarcoma tumors.

ORGANISM(S): Danio rerio

PROVIDER: GSE31185 | GEO | 2011/11/01

SECONDARY ACCESSION(S): PRJNA154077

REPOSITORIES: GEO

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The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes Ewing's-type tumors in zebrafish

Project description:The fusion oncoprotein EWS-FLI1 arises from a t(11;22)(q24;q12) chromosomal translocation and causes Ewing's Sarcoma, a malignant bone tumor. The mechanism whereby EWS-FLI1 transforms cells is unknown. Somatic, mosaic expression of human EWS-FLI1 in zebrafish from the heat shock promoter [Tg(HSP:EWS-FLI1)] caused small round blue cell tumors (SRBCTs) similar to human Ewing's sarcoma. We performed microarray studies comparing zebrafish SRBCTs to another tumor type, zebrafish malignant peripheral nerve sheath tumors (MPNSTs). The results identify a conserved set of EWS-FLI1-regulated genes,and provide insight into the pathogenesis of Ewing's Sarcoma tumors.

2011-11-01 | GSE31186 | GEO

The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes Ewing's-type tumors in zebrafish

2011-11-01 | E-GEOD-31186 | biostudies-arrayexpress

The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes developmental defects in zebrafish embryos

Project description:The fusion oncoprotein EWS-FLI1 arises from a t(11;22)(q24;q12) chromosomal translocation and causes Ewing's Sarcoma, a malignant bone tumor. The mechanism whereby EWS-FLI1 transforms cells is unknown. We made germline transgenic zebrafish expressing human EWS-FLI1 under the control of the heat shock promoter. Induction of EWS-FLI1 expression causes multiple defects in embryonic development. We compared gene expression in control and transgenic EWS-FLI1 zebrafish. The results identify a conserved set of EWS-FLI1-regulated genes, and provide insight into the pathogenesis of Ewing's Sarcoma tumors. We performed heat shock and isolated total RNA for microarray studies comparing wildtype AB strain zebrafish with transgenic zebrafish expressing human EWS-FLI1 [Tg(HSP:EWS-FLI1)]. RNA was biotin-lableled and hybridized to zebrafish-specific Affymetrix arrays.

2011-11-01 | E-GEOD-31185 | biostudies-arrayexpress

A zebrafish transgenic model of Ewing's Sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis

Project description:This SuperSeries is composed of the following subset Series: GSE31185: The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes developmental defects in zebrafish embryos GSE31186: The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes Ewing's-type tumors in zebrafish Refer to individual Series

2011-11-01 | E-GEOD-31217 | biostudies-arrayexpress

A functional liaison between E2F and the aberrant ETS oncogene EWS/FLI1 in Ewing's sarcoma

Project description:Translocations of ETS transcription factors are driver mutations in diverse cancers. We investigated the genomic network of the ETS fusion EWS/FLI1 in Ewing's sarcoma (ESFT) as a model of ETS-driven tumorigenesis. ChIP-Seq and transcriptional analysis identified E2F3 as a principle co-factor of EWSFLI1 defining functionally distinct gene sets. While EWS/FLI1 binding independent of E2F3 predominantly associated with repressed differentiation genes, significant co-localization with E2F3 was discovered at proximal promoters of activated growth-related genes. Thus, EWS/FLI1 promotes oncogenesis by simultaneously perturbing differentiation state and augmenting the expression of genes co-regulated by E2F3. Integration of additional E2F3 and ERG localization data from prostate cancer containing TMPRSS2/ERG verified that the ETS-E2F module is also found in prostate cancer and may be of general relevance to ETS driven cancers. Timecourse with 6 timepoints of a doxicyclin inducible EWS-FLI1 knockdown in the A673 Ewing's Sarcoma celline

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pediatric sarcoma: rhabdomyosarcoma & Ewing's sarcoma

Project description:Affymetrx U95Av2 GeneChip hybridizations, RNA extracted from primary human pediatric alveolar (aRMS) and embryonal (eRMS) rhabdomyosarcoma, plus primary pediatric Ewing's sarcoma (EWS) Keywords = pediatric sarcoma Keywords = Ewing's sarcoma Keywords = rhabdomyosarcoma Keywords: other

2004-03-13 | GSE967 | GEO

Re-activation of EWS-FLI1 suppressed FOXO1 expression as a novel therapeutic strategy for Ewing´s sarcoma

Project description:Transient transfection of a Ewing's Sarcoma cell line expressing type I EWS-FLI1 fusion and doxycycline-inducible short hairpin RNA against EWS-FLI1 (A673sh)

2013-07-01 | GSE37409 | GEO

Danio rerio

Project description:The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes Ewing's-type tumors in zebrafish

| PRJNA154079 | ENA

Re-activation of EWS-FLI1 suppressed FOXO1 expression as a novel therapeutic strategy for EwingÂ´s sarcoma

Project description:Transient transfection of a Ewing's Sarcoma cell line expressing type I EWS-FLI1 fusion and doxycycline-inducible short hairpin RNA against EWS-FLI1 (A673sh) In total, 7 samples were analysed: empty vector control and two nuclear directed AKT- and CDK2- phosphorylation resistant FOXO1 versions as well as sh-scrambled and sh-FOXO1, either in the presence (w.o. Doxy.) or absence of EWS-FLI1 (+ Doxy.) each 2 replicates

2013-07-01 | E-GEOD-37409 | biostudies-arrayexpress

A functional liaison between E2F and the aberrant ETS oncogene EWS/FLI1 in Ewing's sarcoma

2013-07-01 | GSE27524 | GEO

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