| First Author | Sohn EJ | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 3 | Pages | 1154-63 |
| PubMed ID | 20103643 | Mgi Jnum | J:156860 |
| Mgi Id | MGI:4421599 | Doi | 10.1158/0008-5472.CAN-09-1993 |
| Citation | Sohn EJ, et al. (2010) EWS/FLI1 oncogene activates caspase 3 transcription and triggers apoptosis in vivo. Cancer Res 70(3):1154-63 |
| abstractText | 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. |
