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Title: EWS/ATF1 activates Fos and induces soft tissue sarcomas from neural crest-derived cells [Agilent].      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
05-13-2014
ID:
E-GEOD-41122
description:
Clear cell sarcoma (CCS) is an aggressive soft tissue malignant tumor characterized by a unique t(12; 22) translocation, leading to the expression of a chimeric EWS/ATF1 fusion gene. However, little is known about the mechanisms underlying how EWS/ATF1 is involved in the development of CCSs. In addition, the cells of origin for CCSs remain to be determined. We generated EWS/ATF1-inducible mice, and examined the effects of EWS/ATF1 expression in adult cells. We show that the forced expression of EWS/ATF1 results in the development of EWS/ATF1-dependent sarcomas in mice. The histology of EWS/ATF1-induced sarcomas resembles that of CCSs and EWS/ATF1-induced tumor cells express CCS-markers, such as S100, Sox10, and Mitf. A lineage tracing experiment revealed that such sarcomas are derived from neural crest-lineage cells. Finally, we found that EWS/ATF1 directly induces Fos in an ERK-independent manner, and demonstrated that the increased Fos expression is important for the active cell proliferation in not only EWS/ATF1-induced sarcomas, but also in human CCSs. Our results indicate that FOS, as well as EWS/ATF1 itself, could be a promising therapeutic target for the treatment of EWS/ATF1-related sarcomas. Tumor cell lines were established from soft tissue sarcomas in EWS/ATF1-induced mice. Because these cell lines contain doxycycline-inducible EWS/ATF1 alleles, EWS/ATF1 expression can be regulated by the different concentrations of doxycycline. Tumor cell lines were exposed to different concentrations of doxycycline, and total RNAs were isolated at 3 and 48 hours after the doxycycline exposure.
keywords:
transcription profiling by array
format:
HTML
storedIn:
Array Express
qualifier:
not compressed
accessType:
landing page
authorization:
none
authentication:
none
primary:
true
accessURL: https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-41122
format:
JSON
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-41122.json
format:
XML
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: http://www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-41122.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/

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