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Gene expression profile by blocking the SYT-SSX fusion gene in synovial sarcoma cells. Identification of XRCC4 as a putative SYT-SSX target gene

Oncogene volume 22, pages 7628–7631 (2003)Cite this article

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Abstract

Increasing evidence suggests that the SYT-SSX fusion gene plays an important role in synovial sarcoma development and progression. However, very little is known about the downstream targets of SYT-SSX. In this study, we used antisense oligonucleotides to block the expression of the SYT-SSX fusion gene in synovial sarcoma cells. By comparing SYT-SSX inhibited cells with noninhibited cells, the gene expression profile was analysed using cDNA microarray and established by real-time PCR. Herewith, using a filter containing 1176 cancer-relevant genes, we found that the DNA repair gene XRCC4 and the DNA mismatch repair gene MSH2 were downregulated, whereas the gene encoding for the serine/threonine protein kinase PRK (also known as CNK), and the macrophage inhibitory cytokine MICI (also known as PLAB) were upregulated after the inhibition of SYT-SSX. In comparison, expression of the XRCC4 gene was undergoing the strongest alteration. Consistently, the protein expression of XRCC4 was found to be decreased after SYT-SSX inhibition, whereas there were no detectable changes for the other gene products. Our study provides some clues to elucidate the signaling pathways of the SYT-SSX fusion gene, as well as it demonstrates a valuable model system for search for other SYT-SSX targets.

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Acknowledgements

This project was supported by grants from the Swedish Cancer Society, the Stockholm Cancer Society and the Swedish Children Cancer Society.

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Author notes

  1. Yuntao Xie, Maria Törnkvist and Yan Aalto: Equal contribution

Authors and Affiliations

  1. Department of Oncology and Pathology, CCK R8:04, Karolinska Hospital, Stockholm, SE-171 76, Sweden

    Yuntao Xie, Maria Törnkvist, Leonard Girnita & Olle Larsson

  2. Department of Surgery, Beijing Cancer Hospital, School of Oncology, Peking University, Beijing, 100036, China

    Yuntao Xie

  3. Department of Medical Genetics, Haartman Institute and Helsinki University Central Hospital, FIN-00014, University of Helsinki, Helsinki, Finland

    Yan Aalto, Bálint Nagy & Sakari Knuutila

  4. Department of Orthopedics, Karolinska Hospital, Stockholm, SE-171 76, Sweden

    Gunnar Nilsson

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  1. Yuntao Xie
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Correspondence to Sakari Knuutila or Olle Larsson.

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Xie, Y., Törnkvist, M., Aalto, Y. et al. Gene expression profile by blocking the SYT-SSX fusion gene in synovial sarcoma cells. Identification of XRCC4 as a putative SYT-SSX target gene. Oncogene 22, 7628–7631 (2003). https://doi.org/10.1038/sj.onc.1207153

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