 |
 |
GEO help: Mouse over screen elements for information. |
|
| 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 |
| E-mail(s) |
maximilian.kauer@ccri.at
|
| 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)
|
|
| Relations |
| BioProject |
PRJNA120859 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19197_RAW.tar |
35.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...