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 language | English (US) |
|---|---|
| Pages (from-to) | 1536-1540 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 60 |
| Issue number | 6 |
| State | Published - Mar 15 2000 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor β type II receptor gene. / Im, Young Hyuck; Kim, Heung Tae; Lee, Cecile; Poulin, Danielle; Welford, Scott; Sorensen, Poul H.B.; Denny, Christopher T.; Kim, Seong Jin.
In: Cancer Research, Vol. 60, No. 6, 15.03.2000, p. 1536-1540.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor β type II receptor gene
AU - Im, Young Hyuck
AU - Kim, Heung Tae
AU - Lee, Cecile
AU - Poulin, Danielle
AU - Welford, Scott
AU - Sorensen, Poul H.B.
AU - Denny, Christopher T.
AU - Kim, Seong Jin
PY - 2000/3/15
Y1 - 2000/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0342424350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0342424350&partnerID=8YFLogxK
M3 - Article
VL - 60
SP - 1536
EP - 1540
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 6
ER -