Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: EWS/ATF1 activates Fos and induces soft tissue sarcomas [Affymetrix].      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
04-22-2013
ID:
E-GEOD-41121
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 exposed to different concentrations of doxycycline, and total RNAs were isolated at 24 hours after the doxycycline exposure. Total RNAs were also isolated directly from a tumor developed in a EWS/ATF1-inducible mouse given doxycycline for 3 months. The doxycycline concentration and time point for each sample is EWS-ATF1_control; 0 microg/ml (no dox), 24 hours after the exposure, EWS-ATF1_24h_highDox; 0.2 microg/ml, 24 hours after the exposure and EWS-ATF1_tumor1; a tumor was resected from a EWS/ATF1-inducible mouse given doxycycline for 3 months.
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-41121
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-41121.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-41121.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/

Feedback?

If you are having problems using our tools, or if you would just like to send us some feedback, please post your questions on GitHub.