Abstract
Ewing sarcoma is a cancer of bone and soft tissue in children that is characterized by a chromosomal translocation involving EWS and an Ets family transcription factor, most commonly FLI-1. The EWS-FLI-1 fusion oncogene is widely believed to play a central role in Ewing sarcoma. The EWS-FLI-1 gene product regulates the expression of a number of genes important for cancer progression, can transform mouse cells such as NIH3T3 and C3H10T1/2, and is necessary for proliferation and tumorigenicity of Ewing sarcoma cells, suggesting that EWS-FLI-1 is the causative oncogene. However, a variety of evidence also suggest that EWS-FLI-1 alone cannot fully explain the Ewing sarcomagenesis. Here we report that FLI-1-EWS, a fusion gene reciprocal to EWS-FLI-1, is frequently expressed in Ewing sarcoma. We present evidence suggesting that endogenous FLI-1-EWS is required for Ewing sarcoma growth and that FLI-1-EWS cooperates with EWS-FLI-1 in human mesenchymal stem cells, putative cells of origin of Ewing sarcoma, through abrogation of the proliferation arrest induced by EWS- FLI-1.
Highlights
Ewing sarcoma is an aggressive cancer of bone and soft tissues in children with poor long-term outcome
We present evidence suggesting that endogenous FLI-1-EWS is required for Ewing sarcoma growth and that FLI-1-EWS cooperates with EWS-FLI-1 in human mesenchymal stem cells, putative cells of origin of Ewing sarcoma, through abrogation of the proliferation arrest induced by EWSFLI-1
Previous studies failed to detect the expression of FLI-1EWS in Ewing sarcoma by Northern blotting [6, 13, 14], we became interested in the possibility that FLI-1-EWS is expressed in some Ewing sarcoma cells or was expressed when the EWS-FLI-1 chromosomal translocation occurred in the Ewing sarcoma cell of origin
Summary
Ewing sarcoma is an aggressive cancer of bone and soft tissues in children with poor long-term outcome. We present evidence suggesting that endogenous FLI-1-EWS is required for Ewing sarcoma growth and that FLI-1-EWS cooperates with EWS-FLI-1 in human mesenchymal stem cells, putative cells of origin of Ewing sarcoma, through abrogation of the proliferation arrest induced by EWSFLI-1. Using two different pairs of PCR primers (#1 and #2, see Figure 1A), we were able to detect the FLI-1-EWS fusion transcript in A673 and CHLA-9, but not in TC71 Ewing sarcoma cells
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