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

Publication TypeJournal Article
AuthorsSmith, Richard, Owen Leah A., Trem Deborah J., Wong Jenny S., Whangbo Jennifer S., Golub Todd R., and Lessnick Stephen L.
AbstractOur 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 Publication2006
JournalCancer Cell
Volume9
Issue5
Pages405 - 16
Date Published (YYYY/MM/DD)2006/05//
ISBN Number1535-6108
KeywordsAnimals, Cancer, Cell Transformation, Fusion, Gene Expression Profiling, Gene Expression Regulation, Genes, Homeodomain Proteins, Humans, Mice, Microarray Analysis, Neoplasm, Neoplastic, Nude, Oncogene Proteins, R, Retroviridae, RNA Interference