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

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. 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.

ORGANISM(S): Danio rerio

PROVIDER: GSE31186 | GEO | 2011/11/01

SECONDARY ACCESSION(S): PRJNA154079

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. Zebrafish SRBCTs arising from somatic insertions of the EWS-FLI1 transgene were collected. MPNSTs from non-transgenic fish of the same genetic background were collected in parallel. RNA was prepared from all samples and hybridized to zebrafish-specific Affymetrix arrays.

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

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

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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

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