|Publication Type||Journal Article|
|Year of Publication||2006|
|Authors||Smith, R, Owen, LA, Trem, DJ, Wong, JS, Whangbo, JS, Golub, TR, Lessnick, SL|
|Pages||405 - 16|
|Keywords||Animals, 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|
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.