• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


EWS/FLI1 oncogene activates caspase 3 transcription and triggers apoptosis in vivo.

EWS/FLI1 is a fusion gene product generated by a chromosomal translocation t(11;22)(q24;q12) found in Ewing sarcoma. EWS/FLI1 encodes an aberrant transcription factor with oncogenic properties in vitro. Paradoxically, expression of EWS/FLI1 in nontransformed primary cells results in apoptosis, but the exact mechanism remains unclear. In primary mouse embryonic fibroblasts derived from conditional EWS/FLI1 knock-in embryos, expression of EWS/FLI1 resulted in apoptosis with concomitant increase in the endogenous Caspase 3 (Casp3) mRNA. EWS/FLI1 directly bound and activated the CASP3 promoter, whereas small interfering RNA-mediated knockdown of EWS/FLI1 led to a marked decrease in CASP3 transcripts in Ewing sarcoma cell lines. Ectopic expression of EWS/FLI1 resulted in an increased expression of CASP3 protein in heterologous cell lines. Importantly, expression of EWS/FLI1 in the mouse triggered an early onset of apoptosis in kidneys and acute lethality. These findings suggest that EWS/FLI1 induces apoptosis, at least partially, through the activation of CASP3 and show the cell context-dependent roles of EWS/FLI1 in apoptosis and tumorigenesis.

Pubmed ID: 20103643


  • Sohn EJ
  • Li H
  • Reidy K
  • Beers LF
  • Christensen BL
  • Lee SB


Cancer research

Publication Data

February 1, 2010

Associated Grants

  • Agency: Intramural NIH HHS, Id: ZIA DK056003-05

Mesh Terms

  • Animals
  • Antineoplastic Agents, Hormonal
  • Apoptosis
  • Base Sequence
  • Binding Sites
  • Caspase 3
  • Cell Line, Tumor
  • Cells, Cultured
  • Embryo, Mammalian
  • Fibroblasts
  • Gene Expression
  • Heart
  • Humans
  • Kidney
  • Lung
  • Mice
  • Mice, Transgenic
  • Myocardium
  • Oncogene Proteins, Fusion
  • Pancreas
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Protein c-fli-1
  • RNA Interference
  • RNA-Binding Protein EWS
  • Tamoxifen
  • Transcription, Genetic