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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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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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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

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Article

Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis

  • Authors:
    • Hiroki Arai
    • Ryuichi Wada
    • Kousuke Ishino
    • Mitsuhiro Kudo
    • Eiji Uchida
    • Zenya Naito
  • View Affiliations / Copyright

    Affiliations: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan, Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8602, Japan
  • Pages: 978-988
    |
    Published online on: January 5, 2018
       https://doi.org/10.3892/ijo.2018.4238
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Abstract

Gastric cancer is the third major cause of cancer-related mortality in Japan. The aim of this study was to identify a factor implicated in the biology of gastric cancer by comprehensive protein profiling. Protein profiling was carried out by liquid chromatography-tandem mass spectrometry, using formalin-fixed paraffin-embedded specimens of 17 gastric cancer cases. Pathway analysis and orthogonal partial least square-discriminant analysis suggested the significant expression of ribonucleoproteins, heterogeneous nuclear ribonucleoproteins, interleukin binding factor 2 (ILF2), KU70 and KU80, which are involved in DNA damage response (DDR). Thus, the expression and phosphorylation levels of KU70, ILF2, CHK1 and CHK2 were examined by immunohistochemistry in 42 cases of gastric cancer. The expressions of ILF2 and CHK1 were unaffected in all cases. The expression and phosphorylation of CHK2 were absent in 2 cases. Despite the expression of proteins, the phosphorylation of KU70 and CHK2 appeared to be impaired in 1 and 4 cases, respectively. In 7 out of 42 cases (17%), DDR appeared to be impaired. Recurrence was noted in 2 out of these 7 cases (29%), whereas the recurrence was noted in 2 out of the remaining 35 cases (6%). The expression levels of KU70, ILF2, CHK1, CHK2 and TP53 were further examined in 4 gastric cancer cell lines. The expression and phosphorylation levels following exposure to ultraviolet radiation were abnormal in the 3 cell lines. The normal consecutive phosphorylation of CHK1 and CHK2, the upregulation of TP53 and an increase in apoptotic cell death following exposure to ultraviolet radiation was detected only in one cell line, suggesting that the preserved functions of DDR and TP53 are necessary for the determination of cell fate. It is thus suggested that DDR plays an important role in the pathobiology of gastric cancers.
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Copy and paste a formatted citation
Spandidos Publications style
Arai H, Wada R, Ishino K, Kudo M, Uchida E and Naito Z: Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis. Int J Oncol 52: 978-988, 2018.
APA
Arai, H., Wada, R., Ishino, K., Kudo, M., Uchida, E., & Naito, Z. (2018). Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis. International Journal of Oncology, 52, 978-988. https://doi.org/10.3892/ijo.2018.4238
MLA
Arai, H., Wada, R., Ishino, K., Kudo, M., Uchida, E., Naito, Z."Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis". International Journal of Oncology 52.3 (2018): 978-988.
Chicago
Arai, H., Wada, R., Ishino, K., Kudo, M., Uchida, E., Naito, Z."Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis". International Journal of Oncology 52, no. 3 (2018): 978-988. https://doi.org/10.3892/ijo.2018.4238
Copy and paste a formatted citation
x
Spandidos Publications style
Arai H, Wada R, Ishino K, Kudo M, Uchida E and Naito Z: Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis. Int J Oncol 52: 978-988, 2018.
APA
Arai, H., Wada, R., Ishino, K., Kudo, M., Uchida, E., & Naito, Z. (2018). Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis. International Journal of Oncology, 52, 978-988. https://doi.org/10.3892/ijo.2018.4238
MLA
Arai, H., Wada, R., Ishino, K., Kudo, M., Uchida, E., Naito, Z."Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis". International Journal of Oncology 52.3 (2018): 978-988.
Chicago
Arai, H., Wada, R., Ishino, K., Kudo, M., Uchida, E., Naito, Z."Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis". International Journal of Oncology 52, no. 3 (2018): 978-988. https://doi.org/10.3892/ijo.2018.4238
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