Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.
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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
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Journal | Cancer Cell
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Volume | 9
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Issue | 5
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Pages | 405-16
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Date Published | 2006 May
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ISSN | 1535-6108
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URL | |
DOI | 10.1016/j.ccr.2006.04.004
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PubMed ID | 16697960
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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
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