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Series GSE19197 Query DataSets for GSE19197
Status Public on May 26, 2010
Title Hypoxia modulates EWS-FLI1 transcriptional signature and enhances malignant properties of Ewing’s tumor cells in vitro
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Hypoxia is an important condition in the tumor cell microenvironment and approximately 1-1.5% of the genome is transcriptionally responsive to hypoxia with hypoxia-inducible factor-1 (HIF-1) as a major mediator of transcriptional activation. Tumor hypoxia is associated with a more aggressive phenotype of many cancers in adults, but data on pediatric tumors are scarce. By immunohistochemical analysis, HIF-1α expression was readily detectable in 18/28 primary Ewing´s sarcoma family tumors (ESFT), a group of highly malignant bone-associated tumors in children and young adults, which encouraged us to study the effect of hypoxia on ESFT cell lines in vitro.
Many tumors are profoundly hypoxic and multiple studies have demonstrated that hypoxic tumors have a poorer prognosis than non-hypoxic tumors. The cellular adaptations of cancer cells to hypoxia have been shown to profoundly influence transcriptional regulation. Intriguingly, we found that EWS-FLI1 protein expression, which characterizes ESFT, is up-regulated by hypoxia in a HIF-1α-dependent manner. Hypoxia modulated the EWS-FLI1 transcriptional signature relative to normoxic conditions. Both synergistic as well as antagonistic transcriptional effects of EWS-FLI1 and of hypoxia were observed. Consistent with alterations in the expression of metastasis related genes, hypoxia stimulated the invasiveness and soft-agar colony formation of ESFT cells in vitro. Our data represents the first transcriptome analysis of hypoxic ESFT cells and identifies hypoxia as an important microenvironmental factor modulating EWS-FLI1 expression and target gene activity with far-reaching consequences for the malignant properties of ESFT.

Keywords: Consequences on gene expression of hypoxic condition created by exposure of cells to 1% oxygen in a hypoxia chamber.
Overall design We analysed the consequences of hypoxia on gene expression in two ESFT cell lines (SK-N-MC, TC252) grown as multicellular spheroids and as adherent monolayers.
Contributor(s) Aryee DN, Niedan S, Kauer M, Schwentner R, Bennani-Baiti IM, Ban J, Kreppel M, Muehlbacher K, Poremba C, Kofler R, Kovar H, Walker RL, Meltzer PS
Citation(s) 20442286
Submission date Nov 25, 2009
Last update date Mar 25, 2019
Contact name Maximilian Kauer
Organization name CCRI, St.Anna Children Cancer Research Institute
Department Molecular Biology
Lab Heinrich Kovar
Street address Zimmermannplatz 10
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (2)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (12)
GSM475944 sknmc.normoxia.adherent.1
GSM475945 tc252.normoxia.adherent.1
GSM475946 sknmc.hypoxia.adherent.1
BioProject PRJNA120859

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE19197_RAW.tar 35.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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