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

Oncogene volume 18, pages 3303–3308 (1999)Cite this article

Abstract

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

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Acknowledgements

We thank J Milbrandt for the p(B1a)8-Luc vector and EW Khandjian for critical reading of the manuscript. This work was supported by a grant from the Medical Research Council of Canada to Yves Labelle (MT-13644). Yves Labelle is the recipient of a junior scientist fellowship from the Fonds de la recherche en santé du Québec, and Frank Courjal was supported by a fellowship from the Ministère de l'Education du Québec.

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Authors and Affiliations

  1. Unité de recherche en génétique humaine et moléculaire, Pavillon Saint-François d'Assise, CHUQ, Québec (Qc), G1L 3L5, Canada

    Yves Labelle, Johanne Bussières & Frank Courjal

  2. Faculté de Médecine de l'Université Laval, Ste-Foy (Qc), G1K 7P4, Canada

    Yves Labelle, Johanne Bussières & Frank Courjal

  3. Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, 02115, Massachusetts, USA

    Mary B Goldring

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  1. Yves Labelle
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Labelle, Y., Bussières, J., Courjal, F. et al. The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator. Oncogene 18, 3303–3308 (1999). https://doi.org/10.1038/sj.onc.1202675

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