Our hosting provider will be undergoing maintenance on Tuesday, August 30 between 8am and 5pm PDT. SciCrunch services may be offline during the maintenance.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

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

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

Authors

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

Journal

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