The EWS TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator

The EWS/TEC gene fusion generated by the t(9;22) chromosomal translocation found in extraskeletal myxoid chondrosarcomas encodes a fusion protein cont aining the amino-terminal domain of the EWS protein fused to the whole codi ng sequence of the orphan nuclear receptor TEC. We have compared the DNA-bi nding and transcriptional activation properties of various TEC isoforms and the corresponding EWS/TEC fusion proteins. Band-shift experiments show tha t the full-length TEC receptor can efficiently bind the NGFI-B Response Ele ment (NBRE), whereas an isoform lacking the entire carboxyl-terminal domain of the receptor binds much less efficiently the NBRE, Addition of the amin oterminal domain of EWS to either isoforms does not alter significantly the ir DNA-binding properties to the NBRE, Co-transfection experiments of COS c ells and human chondrocytes indicate that whereas TEC moderately activates transcription from a NBRE-containing promoter, the corresponding EWS/TEC fu sion protein is a highly potent transcriptional activator of the same promo ter, being approximately 270-fold more active than the native receptor. EWS /TEC may thus exert its oncogenic potential in chrondrosarcomas by activati ng the transcription of target genes involved in cell proliferation.