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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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April 2013 Volume 42 Issue 4

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International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Article

Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody

  • Authors:
    • Yonghzong Wu
    • Smitha Antony
    • Stephen M. Hewitt
    • Guojian Jiang
    • Sherry X. Yang
    • Jennifer L. Meitzler
    • Agnes Juhasz
    • Jiamo Lu
    • Han Liu
    • James H. Doroshow
    • Krishnendu Roy
  • View Affiliations / Copyright

    Affiliations: Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
  • Pages: 1229-1238
    |
    Published online on: February 11, 2013
       https://doi.org/10.3892/ijo.2013.1821
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Abstract

Dual oxidase 2 (Duox2), one of the seven members of the NADPH oxidase gene family, plays a critical role in generating H2O2 for thyroid hormone biosynthesis and as an integral part of the host defense system of the respiratory epithelium and the gastrointestinal tract. Recent evidence suggests that the regulation of Duox2 expression is under the control of pro-inflammatory cytokines and that Duox2-induced reactive oxygen species (ROS) contribute to the inflammation-related tissue injury that occurs in two pre-malignant, inflammatory conditions: chronic pancreatitis and inflammatory bowel disease. Because no reliable Duox antibodies are commercially available, we report the development of a murine monoclonal antibody (MAb) to Duox2 (clone Duox S-12) and its use for the characterization of Duox2 expression in human tumors, tumor cell lines and normal tissues. Duox S-12 specifically detected both endogenously- and ectopically-expressed Duox2 protein by immunoblotting, immunofluorescence microscopy and immunohistochemistry (where both membranous and cytoplasmic staining were present). Duox2 expression detected by Duox S-12 was functionally coupled to the generation of H2O2 in pancreatic cancer cells that expressed Duox2 and its cognate maturation factor DuoxA2. Although Duox S-12 recognizes ectopically expressed Duox1 protein because of the extensive amino acid homology between Duox1 and Duox2, the lack of substantial Duox1 mRNA expression in human tumors (except thyroid cancer) allowed us to evaluate Duox2 expression across a wide range of normal and malignant tissues by immuno­histochemistry. Duox2 was expressed at elevated levels in many human cancers, most notably tumors of the prostate, lung, colon and breast while brain tumors and lymphomas demonstrated the lowest frequency of expression. The Duox-specific monoclonal antibody described here provides a promising tool for the further examination of the role of Duox-dependent reactive oxygen production in inflammation-related carcinogenesis, where alterations in oxidant tone play a critical role in cell growth and proliferation.
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Copy and paste a formatted citation
Spandidos Publications style
Wu Y, Antony S, Hewitt SM, Jiang G, Yang SX, Meitzler JL, Juhasz A, Lu J, Liu H, Doroshow JH, Doroshow JH, et al: Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody. Int J Oncol 42: 1229-1238, 2013.
APA
Wu, Y., Antony, S., Hewitt, S.M., Jiang, G., Yang, S.X., Meitzler, J.L. ... Roy, K. (2013). Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody. International Journal of Oncology, 42, 1229-1238. https://doi.org/10.3892/ijo.2013.1821
MLA
Wu, Y., Antony, S., Hewitt, S. M., Jiang, G., Yang, S. X., Meitzler, J. L., Juhasz, A., Lu, J., Liu, H., Doroshow, J. H., Roy, K."Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody". International Journal of Oncology 42.4 (2013): 1229-1238.
Chicago
Wu, Y., Antony, S., Hewitt, S. M., Jiang, G., Yang, S. X., Meitzler, J. L., Juhasz, A., Lu, J., Liu, H., Doroshow, J. H., Roy, K."Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody". International Journal of Oncology 42, no. 4 (2013): 1229-1238. https://doi.org/10.3892/ijo.2013.1821
Copy and paste a formatted citation
x
Spandidos Publications style
Wu Y, Antony S, Hewitt SM, Jiang G, Yang SX, Meitzler JL, Juhasz A, Lu J, Liu H, Doroshow JH, Doroshow JH, et al: Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody. Int J Oncol 42: 1229-1238, 2013.
APA
Wu, Y., Antony, S., Hewitt, S.M., Jiang, G., Yang, S.X., Meitzler, J.L. ... Roy, K. (2013). Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody. International Journal of Oncology, 42, 1229-1238. https://doi.org/10.3892/ijo.2013.1821
MLA
Wu, Y., Antony, S., Hewitt, S. M., Jiang, G., Yang, S. X., Meitzler, J. L., Juhasz, A., Lu, J., Liu, H., Doroshow, J. H., Roy, K."Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody". International Journal of Oncology 42.4 (2013): 1229-1238.
Chicago
Wu, Y., Antony, S., Hewitt, S. M., Jiang, G., Yang, S. X., Meitzler, J. L., Juhasz, A., Lu, J., Liu, H., Doroshow, J. H., Roy, K."Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody". International Journal of Oncology 42, no. 4 (2013): 1229-1238. https://doi.org/10.3892/ijo.2013.1821
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