[PDF][PDF] Expression profiling of EWS/FLI identifies NKX2. 2 as a critical target gene in Ewing's sarcoma
R Smith, LA Owen, DJ Trem, JS Wong, JS Whangbo… - Cancer cell, 2006 - cell.com
Cancer cell, 2006•cell.com
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 …
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 …
Summary
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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