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A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity

Oncogene volume 26, pages 1178–1187 (2007)Cite this article

Abstract

Anaplastic thyroid cancer (ATC) is one of the most lethal of all human tumors, but cytogenetic information concerning ATC is extremely limited. Using our in-house array-based comparative genomic hybridization and 14 ATC cell lines with further fluorescence in situ hybridization analysis, we demonstrated amplification of the DUSP26 gene, known by another report as MAP kinase phosphatase-8. DUSP26 was overexpressed in ATC cell lines and primary ATC tumor samples. When overexpressed, either exogenously or endogenously, DUSP26 promoted growth of the ATC cells. DUSP26 encodes a protein containing a dual-specificity phosphatase domain that can dephosphorylate itself. DUSP26 effectively dephosphorylates p38 and has a little effect on extracellular signal-regulated kinase in ATC cells. DUSP26 protein formed a physical complex with p38, and promoted survival of ATC cells by inhibiting p38-mediated apoptosis. Our findings suggest that DUSP26 may act as an oncogene in ATC, and might be a useful diagnostic marker and therapeutic target of this disease.

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Acknowledgements

We are grateful to Professor Y Nakamura (Human Genome Center, Institute of Medical Science, The University of Tokyo) for continual encouragement throughout this work. This work was supported by grants-in-aid for Scientific Research (to J Inazawa, I Imoto) and Scientific Research on Priority Areas (C) (to J Inazawa, I Imoto), and a 21st Century Center of Excellence (COE) Program for Molecular Destruction and Reconstruction of Tooth and Bone (to J Inazawa, W Yu) from the Ministry of Education, Culture, Sports, Science and Technology, Japan; and a grant from Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST) (to J Inazawa). W Yu is a Heiwa Nakajima Foundation Scholar.

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Authors and Affiliations

  1. Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Biomedical Science, Tokyo, Japan

    W Yu, I Imoto, J Inoue & J Inazawa

  2. 21st Century Center of Excellence (COE) Program for Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo, Japan

    W Yu & J Inazawa

  3. Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan

    I Imoto & J Inazawa

  4. Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Saitama, Japan

    I Imoto, J Inoue & J Inazawa

  5. Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kanagawa, Japan

    M Onda & M Emi

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Correspondence to J Inazawa.

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Yu, W., Imoto, I., Inoue, J. et al. A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity. Oncogene 26, 1178–1187 (2007). https://doi.org/10.1038/sj.onc.1209899

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