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

Cancer Cell. 2006 May;9(5):405-16. doi: 10.1016/j.ccr.2006.04.004.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Neoplasm / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Mice
  • Mice, Nude
  • Microarray Analysis
  • Oncogene Proteins, Fusion / genetics*
  • Proto-Oncogene Protein c-fli-1
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Protein EWS
  • Retroviridae / genetics
  • Sarcoma, Ewing / genetics*
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Zebrafish Proteins

Substances

  • EWS-FLI fusion protein
  • Homeodomain Proteins
  • Nkx2.2 protein
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Protein c-fli-1
  • RNA, Messenger
  • RNA-Binding Protein EWS
  • Transcription Factors
  • Zebrafish Proteins

Associated data

  • GEO/GSE4565