You are here

Cancer Cell DOI:10.1016/j.ccr.2006.04.004

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

Publication TypeJournal Article
Year of Publication2006
AuthorsSmith, R, Owen, LA, Trem, DJ, Wong, JS, Whangbo, JS, Golub, TR, Lessnick, SL
JournalCancer Cell
Date Published2006 May
KeywordsAnimals, Cell Transformation, Neoplastic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Homeodomain Proteins, Humans, Mice, Mice, Nude, Microarray Analysis, Oncogene Proteins, Fusion, Proto-Oncogene Protein c-fli-1, Retroviridae, RNA Interference, RNA, Messenger, RNA-Binding Protein EWS, Sarcoma, Ewing, Transcription Factors, Transcription, Genetic

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.


Alternate JournalCancer Cell
PubMed ID16697960
Grant ListK08 CA096755 / CA / NCI NIH HHS / United States
K08 CA096755-05 / CA / NCI NIH HHS / United States
T32 HD007491 / HD / NICHD NIH HHS / United States
K08 CA96755 / CA / NCI NIH HHS / United States