Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.

Cancer Cell
Authors
Keywords
Abstract

Our understanding of Ewing's sarcoma development mediated by the EWS/FLI fusion protein has been limited by a lack of knowledge regarding the tumor cell of origin. To circumvent this, we analyzed the function of EWS/FLI in Ewing's sarcoma itself. By combining retroviral-mediated RNA interference with reexpression studies, we show that ongoing EWS/FLI expression is required for the tumorigenic phenotype of Ewing's sarcoma. We used this system to define the full complement of EWS/FLI-regulated genes in Ewing's sarcoma. Functional analysis revealed that NKX2.2 is an EWS/FLI-regulated gene that is necessary for oncogenic transformation in this tumor. Thus, we developed a highly validated transcriptional profile for the EWS/FLI fusion protein and identified a critical target gene in Ewing's sarcoma development.

Year of Publication
2006
Journal
Cancer Cell
Volume
9
Issue
5
Pages
405-16
Date Published
2006 May
ISSN
1535-6108
URL
DOI
10.1016/j.ccr.2006.04.004
PubMed ID
16697960
Links
Grant list
K08 CA096755 / CA / NCI NIH HHS / United States
K08 CA096755-05 / CA / NCI NIH HHS / United States
T32 HD007491 / HD / NICHD NIH HHS / United States
K08 CA96755 / CA / NCI NIH HHS / United States