title: The role of FLI-1-EWS, a fusion gene reciprocal to EWS-FLI-1, in Ewing sarcoma.
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.
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Elzi
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Meihua
authors.initials: M
authors.lastname: Song
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA; Cancer Therapy and Research Center, The University of Texas Health Science Center, San Antonio, Texas, USA; Department of Molecular Medicine, The University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA; Cancer Therapy and Research Center, The University of Texas Health Science Center, San Antonio, Texas, USA; Department of Epidemiology and Biostatistics, The University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA; Cancer Therapy and Research Center, The University of Texas Health Science Center, San Antonio, Texas, USA; Department of Biochemistry, The University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Shiio
keywords: EWS-FLI-1; Ewing sarcoma; FLI-1-EWS