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

Cancer Cell (2006) 9:405-416. Published: 2006.05.15

Richard Smith, Leah A. Owen, Deborah J. Trem, Jenny S. Wong, Jennifer S. Whangbo, Todd R. Golub, and Stephen L. Lessnick

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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.

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Supplemental Data

Description Link/Filename
Manuscript Smith et al.pdf
Preview article Cancer Cell preview.pdf
CEL file descriptions Smith_et_al_CEL_file_list.xls
CEL files for knockdown samples Smith_etal_knockdown_CEL_files.zip
CEL files for inducible samples Smith_etal_inducible_CEL_files.zip
Supplemental appendix 1 Smith, et al., supplemental appendix 1.doc
Supplemental appendix 2 Smith, et al., supplemental appendix 2.xls
Supplemental appendix 3 Smith, et al., supplemental appendix 3.xls