Journal of Gastric Cancer

  • 제13권4호
  • /
  • Pages.232-241
  • /
  • 2013
  • /
  • 2093-582X(pISSN)
  • /
  • 2093-5641(eISSN)
대한위암학회 (The Korean Gastric Cancer Association)
권호 표지
DOI QR코드

DOI QR Code

Gastrokine 1 Expression in the Human Gastric Mucosa Is Closely Associated with the Degree of Gastritis and DNA Methylation

  • Choi, Won Suk (Department of Pathology, The Catholic University of Korea, School of Medicine) ;
  • Seo, Ho Suk (Department of General Surgery, The Catholic University of Korea, School of Medicine) ;
  • Song, Kyo Young (Department of General Surgery, The Catholic University of Korea, School of Medicine) ;
  • Yoon, Jung Hwan (Department of Pathology, The Catholic University of Korea, School of Medicine) ;
  • Kim, Olga (Department of Pathology, The Catholic University of Korea, School of Medicine) ;
  • Nam, Suk Woo (Department of Pathology, The Catholic University of Korea, School of Medicine) ;
  • Lee, Jung Yong (Department of Pathology, The Catholic University of Korea, School of Medicine) ;
  • Park, Won Sang (Department of Pathology, The Catholic University of Korea, School of Medicine)
  • 투고 : 2013.12.02
  • 심사 : 2013.12.20
  • 발행 : 2013.12.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Purpose: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. Materials and Methods: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. Results: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. Conclusions: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.

키워드

참고문헌

  1. Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res 1998;72:141-196.
  2. Leung SY, Yuen ST, Chung LP, Chu KM, Chan AS, Ho JC. hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability. Cancer Res 1999;59:159-164.
  3. Suzuki H, Itoh F, Toyota M, Kikuchi T, Kakiuchi H, Hinoda Y, et al. Distinct methylation pattern and microsatellite instability in sporadic gastric cancer. Int J Cancer 1999;83:309-313. https://doi.org/10.1002/(SICI)1097-0215(19991029)83:3<309::AID-IJC4>3.0.CO;2-Z
  4. Mir MR, Shabir N, Wani KA, Shaff S, Hussain I, Banday MA, et al. Association between p16, hMLH1 and E-cadherin promoter hypermethylation and intake of local hot salted tea and sun-dried foods in Kashmiris with gastric tumors. Asian Pac J Cancer Prev 2012;13:181-186. https://doi.org/10.7314/APJCP.2012.13.1.181
  5. Rocco JW, Sidransky D. p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res 2001;264:42-55. https://doi.org/10.1006/excr.2000.5149
  6. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991;251:1451-1455. https://doi.org/10.1126/science.2006419
  7. Pignatelli M, Vessey CJ. Adhesion molecules: novel molecular tools in tumor pathology. Hum Pathol 1994;25:849-856. https://doi.org/10.1016/0046-8177(94)90002-7
  8. Chan AO, Lam SK, Wong BC, Wong WM, Yuen MF, Yeung YH, et al. Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut 2003;52:502-506. https://doi.org/10.1136/gut.52.4.502
  9. Fleisher AS, Esteller M, Tamura G, Rashid A, Stine OC, Yin J, et al. Hypermethylation of the hMLH1 gene promoter is associated with microsatellite instability in early human gastric neoplasia. Oncogene 2001;20:329-335. https://doi.org/10.1038/sj.onc.1204104
  10. Jin B, Yao B, Li JL, Fields CR, Delmas AL, Liu C, et al. DNMT1 and DNMT3B modulate distinct polycomb-mediated histone modifications in colon cancer. Cancer Res 2009;69:7412-7421. https://doi.org/10.1158/0008-5472.CAN-09-0116
  11. Zhou Y, Du WD, Wu Q, Liu Y, Chen G, Ruan J, et al. EZH2 genetic variants affect risk of gastric cancer in the Chinese Han population. Mol Carcinog 2012 [Epub ahead of print].
  12. Choi JH, Song YS, Yoon JS, Song KW, Lee YY. Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancer. APMIS 2010;118:196-202 https://doi.org/10.1111/j.1600-0463.2009.02579.x
  13. Park SY, Yoo EJ, Cho NY, Kim N, Kang GH. Comparison of CpG island hypermethylation and repetitive DNA hypomethylation in premalignant stages of gastric cancer, stratified for Helicobacter pylori infection. J Pathol 2009;219:410-416. https://doi.org/10.1002/path.2596
  14. Martin TE, Powell CT, Wang Z, Bhattacharyya S, Walsh-Reitz MM, Agarwal K, et al. A novel mitogenic protein that is highly expressed in cells of the gastric antrum mucosa. Am J Physiol Gastrointest Liver Physiol 2003;285:G332-G343. https://doi.org/10.1152/ajpgi.00453.2002
  15. Toback FG, Walsh-Reitz MM, Musch MW, Chang EB, Del Valle J, Ren H, et al. Peptide fragments of AMP-18, a novel secreted gastric antrum mucosal protein, are mitogenic and motogenic. Am J Physiol Gastrointest Liver Physiol 2003;285:G344-G353. https://doi.org/10.1152/ajpgi.00455.2002
  16. Walsh-Reitz MM, Huang EF, Musch MW, Chang EB, Martin TE, Kartha S, et al. AMP-18 protects barrier function of colonic epithelial cells: role of tight junction proteins. Am J Physiol Gastrointest Liver Physiol 2005;289:G163-G171. https://doi.org/10.1152/ajpgi.00013.2005
  17. Yoon JH, Choi YJ, Choi WS, Ashktorab H, Smoot DT, Nam SW, et al. GKN1-miR-185-DNMT1 axis suppresses gastric carcinogenesis through regulation of epigenetic alteration and cell cycle. Clin Cancer Res 2013;19:4599-4610. https://doi.org/10.1158/1078-0432.CCR-12-3675
  18. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996;20:1161-1181.
  19. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001;29:e45. https://doi.org/10.1093/nar/29.9.e45
  20. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A 1996;93:9821- 9826. https://doi.org/10.1073/pnas.93.18.9821
  21. Wang F, Meng W, Wang B, Qiao L. Helicobacter pyloriinduced gastric inflammation and gastric cancer. Cancer Lett 2013 [Epub ahead of print].
  22. Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H, Maekita T, et al. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res 2010;70:1430-1440. https://doi.org/10.1158/0008-5472.CAN-09-2755
  23. Jun KH, Won YS, Shin EY, Cho HM, Im MG, Chin HM, et al. DNA methylation of multiple genes in gastric cancer: association with CpG island methylator phenotype and Helicobacter pylori infection. J Korean Gastric Cancer Assoc 2006;6:227-236 https://doi.org/10.5230/jkgca.2006.6.4.227
  24. Fox JG, Wang TC. Helicobacter pylori--not a good bug after all! N Engl J Med 2001;345:829-832. https://doi.org/10.1056/NEJM200109133451111
  25. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996;87:2095-2147.
  26. Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 2005;5:749-759. https://doi.org/10.1038/nri1703
  27. Yoon JH, Cho ML, Choi YJ, Back JY, Park MK, Lee SW, et al. Gastrokine 1 regulates NF-${\kappa}B$ signaling pathway and cytokine expression in gastric cancers. J Cell Biochem 2013;114:1800- 1809. https://doi.org/10.1002/jcb.24524
  28. Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, et al. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 2006;12:989-995. https://doi.org/10.1158/1078-0432.CCR-05-2096
  29. Nakajima T, Maekita T, Oda I, Gotoda T, Yamamoto S, Umemura S, et al. Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers. Cancer Epidemiol Biomarkers Prev 2006;15:2317-2321. https://doi.org/10.1158/1055-9965.EPI-06-0436
  30. Yoon JH, Song JH, Zhang C, Jin M, Kang YH, Nam SW, et al. Inactivation of the Gastrokine 1 gene in gastric adenomas and carcinomas. J Pathol 2011;223:618-625. https://doi.org/10.1002/path.2838

피인용 문헌

  1. The Role of Gastrokine 1 in Gastric Cancer vol.14, pp.3, 2014, https://doi.org/10.5230/jgc.2014.14.3.147
  2. Gastrokine 1 induces senescence and apoptosis through regulating telomere length in gastric cancer vol.5, pp.22, 2014, https://doi.org/10.18632/oncotarget.2586
  3. Inactivation of NKX6.3 in the stomach leads to abnormal expression of CDX2 and SOX2 required for gastric-to-intestinal transdifferentiation vol.29, pp.2, 2013, https://doi.org/10.1038/modpathol.2015.150
  4. Epigenetic alterations of gastrokine 1 gene expression in gastric cancer vol.8, pp.10, 2013, https://doi.org/10.18632/oncotarget.14817
  5. NKX6.3 protects against gastric mucosal atrophy by downregulating β-amyloid production vol.25, pp.3, 2013, https://doi.org/10.3748/wjg.v25.i3.330
  6. The Complex Network between MYC Oncogene and microRNAs in Gastric Cancer: An Overview vol.21, pp.5, 2013, https://doi.org/10.3390/ijms21051782
  7. The potential function of IKKα in gastric precancerous lesion via mediating Maspin vol.65, pp.None, 2013, https://doi.org/10.1016/j.tice.2020.101349