EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor β type II receptor gene

Young Hyuck Im, Heung Tae Kim, Cecile Lee, Danielle Poulin, Scott Welford, Poul H.B. Sorensen, Christopher T. Denny, Seong Jin Kim

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Ewing sarcoma-specific chromosomal translocations fuse the EWS gene to a subset of ets transcription factor family members, most commonly the FLI1 gene and less frequently ERG, ETV1, EIA-F, or FEV. These fusion proteins are thought to act as aberrant transcription factors that bind DNA through their ets DNA binding domain. Recently, we have shown (K-B. Hahm et al., Nat. Genet., 23: 222-227, 1999) that the transforming growth factor β (TGF-β) type II receptor (TGF-β RII), a putative tumor suppressor gene, is a target of the EWS-FLI1 fusion protein. Here, we also examined effects of EWS-ETV1 and EWS-ERG on expression of the TGF-β RII gene. We show that relative to the control, NIH-3T3 cell lines stably transfected with the EWS-FLI1, EWS- ERG, or EWS-ETV1 gene fusion express reduced levels of TGF-β RII mRNA and protein, and that these cell lines have reduced TGF-β sensitivity. Cotransfection of these fusion genes and the TGF-β RII promoter suppresses TGF-β RII promoter activity and also FLI1-, ERG-, or ETV1-induced promoter activity. These results indicate that transcriptional repression of TGF-β RII is an important target of the EWS-FLI1, EWS-ERG, or EWS-ETV1 oncogene, and that EWS-ets fusion proteins may function as dominant negative forms of ets transcription factors.

Original languageEnglish (US)
Pages (from-to)1536-1540
Number of pages5
JournalCancer Research
Volume60
Issue number6
StatePublished - Mar 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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