Asian Pacific Journal of Cancer Prevention

  • 제16권15호
  • /
  • Pages.6335-6338
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  • 2015
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Expression of Cytoplasmic 8-oxo-Gsn and MTH1 Correlates with Pathological Grading in Human Gastric Cancer

  • Song, Wen-Jie (Department of Gastrointestinal Surgery, the Second Hospital of Wenzhou Medical University) ;
  • Jiang, Ping (The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health) ;
  • Cai, Jian-Ping (The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health) ;
  • Zheng, Zhi-Qiang (Department of Gastrointestinal Surgery, the Second Hospital of Wenzhou Medical University)
  • 발행 : 2015.10.06
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Background: Cancers have dysfunctional redox regulation resulting in production of reactive oxygen species (ROS), damaging DNA, RNA and free NTPs, and causing the accumulation of oxidative nucleic acids in cytoplasm. The major types are 8-oxo-7,8-dihydroguanine(8-oxoGsn) in RNA and 8-oxo-7,8-dihydro-2' deoxyguanosine(8-oxodGsn) in Mt-DNA. The MTH1 protein sanitizes oxidized nucleotide pools from NTPs to monophosphates, preventing the occurrence of transversion mutations. This study concerned cytoplasmic 8-oxodGsn/Gsn and MTH1 expression in gastric cancer and para-cancer tissues and elucidated roles of nucleic-acid oxidation and anti-oxidation. Materials and Methods: A polymer HRP detection system was used to detect 8-oxo-Gsn/dGsn and MTH1 expression in 51 gastric cancer and para-cancer tissue samples. Analyses of patient clinical and pathological data were also performed. Results: The expression of MTH1 and the 8-oxo-dGsn/Gsn ratio were significantly higher in cancer tissues than para-cancer tissues (P<0.05). Cytoplasmic 8-oxo-Gsn and MTH1 were both found to positively correlate (P<0.05) with tumor differentiation, while no significant associations were found with gender, age, invasion depth, lymph node metastasis and clinical stage (P>0.05). Conclusions: We found 8-oxo-dGsn/Gsn and MTH1 are both highly expressed in gastric cancer tissues, especially in well differentiated lesions. In addition, oxidated mtDNA is prevalently expressed in gastric cancers, while 8-oxo-Gsn expression in cytoplasmic RNA is a bit lower, but more selectively.

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참고문헌

  1. Cai JP, Kawate H, Ihara K, et al (1997). Significance of the conserved amino acid sequence for human MTH1 protein with antimutator activity. Nucleic Acids Res, 25, 1170-6. https://doi.org/10.1093/nar/25.6.1170
  2. Cerutti PA (1994). Oxy-radicals and cancer. Lancet, 344, 862-3. https://doi.org/10.1016/S0140-6736(94)92832-0
  3. Trachootham D, Zhou Y, Zhang H, et al (2006). Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell, 10, 241-52. https://doi.org/10.1016/j.ccr.2006.08.009
  4. Woo DK, Green PD, Santos JH, et al (2012). Mitochondrial genome instability and ROS enhance intestinal tumorigenesis in APC (Min/+) mice. Am J Pathol, 180, 24-31. https://doi.org/10.1016/j.ajpath.2011.10.003
  5. Feig DI, Reid TM, Loeb LA (1994). Reactive oxygen species in tumorigenesis. Cancer Res, 54, 1890-4.
  6. Golstein P, Kroemer G (2007). Cell death by necrosis:Towards a molecular definition. Trends Biochem Sci, 32, 37-43. https://doi.org/10.1016/j.tibs.2006.11.001
  7. Guyton KZ, Kensler TW (1993). Oxidative mechanisms in carcinogenesis. Brit Med Bull, 49, 523-44.
  8. Green DR, Reed JC (1998) Mitochondria and apoptosis. Sci, 281, 1309-12. https://doi.org/10.1126/science.281.5381.1309
  9. Saffran HA, Pare JM, Corcoran JA, Weller SK, Smiley JR (2006). Herpes simplex virus eliminates host mitochondrial DNA. EMBO Rep, 8, 188-93.
  10. Helge Gad, Tobias Koolmeister, Ann-Sofie Jemth, et al (2014). MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature, 508, 215-21. https://doi.org/10.1038/nature13181
  11. Saffran HA, Pare JM, Corcoran JA, Weller SK, Smiley JR (2006). Herpes simplex virus eliminates host mitochondrial DNA. EMBO Rep, 8, 188-93.
  12. Kosuke Kajitani, Hiroo Yamaguchi, Yukihiko Dan (2006). MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity. J Neurosci, 26, 1688-98. https://doi.org/10.1523/JNEUROSCI.4948-05.2006
  13. Huber KV, Salah E, Radic B, et al (2014). Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature 508, 222-7. https://doi.org/10.1038/nature13194
  14. Kennedy CH, Pass HI, Mitchell JB (2003). Expression of human MutT homologue (hMTH1) protein in primary non-samall-cell lung carcinomas and histologically normal surrounding tissue. Free Radic Biol Med, 34, 1447-57. https://doi.org/10.1016/S0891-5849(03)00176-X
  15. Koketsu S1, Watanabe T, Nagawa H (2004). Expression of DNA repair protein:MYH, NTH1 and MTH1 in colorectal cancer. Hepatogastroenterol, 51, 638-42.
  16. Clay Montier LL, Deng JJ, Bai Y (2009). Number matters: control of mammalian mitochondrial DNA copy number. J Genet Genomics, 36, 125-31. https://doi.org/10.1016/S1673-8527(08)60099-5
  17. Levine B and Kroemer G (2008). Autophagy in the pathogenesisof disease. Cell, 132, 27-42. https://doi.org/10.1016/j.cell.2007.12.018
  18. Maki H, Sekiguchi M (1992). MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis.Nature, 355, 273-5. https://doi.org/10.1038/355273a0
  19. Nakabeppu Y, Tsuchimoto D, Furuichi M, Sakumi K (2004). The defense mechanisms in mammalian cells against oxidative damage in nucleic acids and their involvement in the suppression of mutagenesis and cell death. Free Radic Res, 38, 423-9. https://doi.org/10.1080/10715760410001688348
  20. Yadav N, Chandra D (2013). Mitochondrial DNA mutations and breast tumorigenesis. Biochim Biophys Acta, 1836, 336-44.
  21. Okamoto K, Toyokuni S, Kim WJ (1996). Overexpression of human MutT homologue gene messenger RNA renalcell carcinoma:evidence of persistent oxidative stress in cancer. Int J Cancer, 65, 437-41. https://doi.org/10.1002/(SICI)1097-0215(19960208)65:4<437::AID-IJC7>3.0.CO;2-Y
  22. Orrenius S, Gogvadze V, and Zhivotovsky B (2007). Mitochondrialoxidative stress: Implications for cell death. Annu Rev Pharmacol Toxicol, 47, 143-83. https://doi.org/10.1146/annurev.pharmtox.47.120505.105122
  23. Shimura-Miura H, Hattori N, Kang D, et al (1999). Increased 8-oxo-dGTPase in the mitochondria of substantia nigral neurons in Parkinson's disease. Ann Neurol, 46, 920-4. https://doi.org/10.1002/1531-8249(199912)46:6<920::AID-ANA17>3.0.CO;2-R
  24. Song XN, Zhang LQ, Liu DG, et al (2011). Oxidativedamage to RNA and expression patterns of MTH1 in the hippocampi ofsenescence-accelerated SAMP8 mice and Alzheimer's disease patients. Neurochem Res, 36, 1558-65. https://doi.org/10.1007/s11064-011-0484-4
  25. Shibutani S, Takeshita M, Grollman AP (1991). Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature, 349, 431-4. https://doi.org/10.1038/349431a0
  26. Zhu W, Qin W, Bradley P, et al (2005). Mitochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid. Carcinogenesis, 26, 145-52.
  27. Zheng JD, Hei AL, Zuo PP, et al (2009). Age-related alterations in the expression of MTH2 in the hippocampus of the SAMP8mouse with learning and memory deterioration. J Neurol Sci, 287, 188-96. https://doi.org/10.1016/j.jns.2009.07.027

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