NR0B1 Is Required for the Oncogenic Phenotype Mediated by EWS/FLI in Ewing's Sarcoma

摘要: A number of solid tumors, such as alveolar rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma, are associated with recurrent translocation events that encode fusion proteins. Ewing9s sarcoma is a pediatric tumor serves prototype for this class. sarcomas usually harbor the (11;22)(q24;q12) translocation. The t(11;22) encodes EWS/FLI oncoprotein. functions an aberrant transcription factor, but key target genes involved in oncogenesis largely unknown. Although some have been defined, many these identified heterologous model systems uncertain relevance to human disease. To understand function its targets more clinically relevant system, we used retroviral-mediated RNAi “knock-down” protein patient-derived cell lines. By combining transcriptional profiling data from three lines, conserved response EWS/FLI. gene was most reproducibly up-regulated by NR0B1. NR0B1 developmentally important orphan nuclear receptor no previously defined role oncogenesis. We validated EWS/FLI-dysregulated confirmed expression primary samples. Functional studies revealed ongoing required transformed phenotype sarcoma. These define new oncogenic transformation emphasize utility analyzing cells. (Mol Cancer Res 2006;4(11):851–7)