Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma - PubMed (original) (raw)

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

Richard Smith et al. Cancer Cell. 2006 May.

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Erratum in

• Cancer Cell. 2007 Jan;11(1):97

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.

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Comment in

• Ewing's sarcoma: general insights from a rare model.
  Davis S, Meltzer PS. Davis S, et al. Cancer Cell. 2006 May;9(5):331-2. doi: 10.1016/j.ccr.2006.05.003. Cancer Cell. 2006. PMID: 16697953

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