Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Infectious Agents and Cancer
Published in: Infectious Agents and Cancer 1/2010

Open Access 01-12-2010 | Research article

Epstein-Barr virus-specific methylation of human genes in gastric cancer cells

Authors: Julie L Ryan, Richard J Jones, Shannon C Kenney, Ashley G Rivenbark, Weihua Tang, Elizabeth RW Knight, William B Coleman, Margaret L Gulley

Published in: Infectious Agents and Cancer | Issue 1/2010

Login to get access

Abstract

Background

Epstein-Barr Virus (EBV) is found in 10% of all gastric adenocarcinomas but its role in tumor development and maintenance remains unclear. The objective of this study was to examine EBV-mediated dysregulation of cellular factors implicated in gastric carcinogenesis.

Methods

Gene expression patterns were examined in EBV-negative and EBV-positive AGS gastric epithelial cells using a low density microarray, reverse transcription PCR, histochemical stains, and methylation-specific DNA sequencing. Expression of PTGS2 (COX2) was measured in AGS cells and in primary gastric adenocarcinoma tissues.

Results

In array studies, nearly half of the 96 human genes tested, representing 15 different cancer-related signal transduction pathways, were dysregulated after EBV infection. Reverse transcription PCR confirmed significant impact on factors having diverse functions such as cell cycle regulation (IGFBP3, CDKN2A, CCND1, HSP70, ID2, ID4), DNA repair (BRCA1, TFF1), cell adhesion (ICAM1), inflammation (COX2), and angiogenesis (HIF1A). Demethylation using 5-aza-2'-deoxycytidine reversed the EBV-mediated dysregulation for all 11 genes listed here. For some promoter sequences, CpG island methylation and demethylation occurred in an EBV-specific pattern as shown by bisulfite DNA sequencing. Immunohistochemistry was less sensitive than was western blot for detecting downregulation of COX2 upon EBV infection. Virus-related dysregulation of COX2 levels in vitro was not recapitulated in vivo among naturally infected gastric cancer tissues.

Conclusions

EBV alters human gene expression in ways that could contribute to the unique pathobiology of virus-associated cancer. Furthermore, the frequency and reversability of methylation-related transcriptional alterations suggest that demethylating agents have therapeutic potential for managing EBV-related carcinoma.
Appendix
Available only for authorised users
Literature
1.
Correa P, Piazuelo MB, Camargo MC: The future of gastric cancer prevention. Gastric Cancer. 2004, 7: 9-16. 10.1007/s10120-003-0265-0.PubMedCrossRef
2.
Gulley ML, Pulitzer DR, Eagan PA, Schneider BG: Epstein-Barr virus infection is an early event in gastric carcinogenesis and is independent of bcl-2 expression and p53 accumulation. Hum Pathol. 1996, 27: 20-27. 10.1016/S0046-8177(96)90133-1.PubMedCrossRef
3.
Murphy G, Pfeiffer R, Camargo MC, Rabkin CS: Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology. 2009, 137: 824-833. 10.1053/j.gastro.2009.05.001.PubMedPubMedCentralCrossRef
4.
Lee JH, Kim SH, Han SH, An JS, Lee ES, Kim YS: Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis. J Gastroenterol Hepatol. 2009, 24: 354-365. 10.1111/j.1440-1746.2009.05775.x.PubMedCrossRef
5.
Cho HJ, Kim JY, Yoo J, Lee SS: Gastric carcinoma with lymphoid stroma: incidence of EBV and Helicobacter pylori infection. Appl Immunohistochem Mol Morphol. 2003, 11: 149-152.PubMedCrossRef
6.
Fukayama M, Chong JM, Uozaki H: Pathology and molecular pathology of Epstein-Barr virus-associated gastric carcinoma. Curr Top Microbiol Immunol. 2001, 258: 91-102.PubMed
7.
Nakamura S, Ueki T, Yao T, Ueyama T, Tsuneyoshi M: Epstein-Barr virus in gastric carcinoma with lymphoid stroma. Special reference to its detection by the polymerase chain reaction and in situ hybridization in 99 tumors, including a morphologic analysis. Cancer. 1994, 73: 2239-2249. 10.1002/1097-0142(19940501)73:9<2239::AID-CNCR2820730902>3.0.CO;2-#.PubMedCrossRef
8.
van Beek J, zur Hausen A, Klein Kranenbarg E, van de Velde CJ, Middeldorp JM, van den Brule AJ, Meijer CJ, Bloemena E: EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement. J Clin Oncol. 2004, 22: 664-670. 10.1200/JCO.2004.08.061.PubMedCrossRef
9.
Zazula M, Ferreira AM, Czopek JP, Kolodziejczyk P, Sinczak-Kuta A, Klimkowska A, Wojcik P, Okon K, Bialas M, Kulig J, Stachura J: CDH1 gene promoter hypermethylation in gastric cancer: relationship to Goseki grading, microsatellite instability status, and EBV invasion. Diagn Mol Pathol. 2006, 15: 24-29. 10.1097/00019606-200603000-00004.PubMedCrossRef
10.
Vauhkonen M, Vauhkonen H, Sipponen P: Pathology and molecular biology of gastric cancer. Best Pract Res Clin Gastroenterol. 2006, 20: 651-674. 10.1016/j.bpg.2006.03.016.PubMedCrossRef
11.
Chang MS, Uozaki H, Chong JM, Ushiku T, Sakuma K, Ishikawa S, Hino R, Barua RR, Iwasaki Y, Arai K, Fujii H, Nagai H, Fukayama M: CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Clin Cancer Res. 2006, 12: 2995-3002. 10.1158/1078-0432.CCR-05-1601.PubMedCrossRef
12.
Sudo M, Chong JM, Sakuma K, Ushiku T, Uozaki H, Nagai H, Funata N, Matsumoto Y, Fukayama M: Promoter hypermethylation of E-cadherin and its abnormal expression in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer. 2004, 109: 194-199. 10.1002/ijc.11701.PubMedCrossRef
13.
Lee HS, Chang MS, Yang HK, Lee BL, Kim WH: Epstein-barr virus-positive gastric carcinoma has a distinct protein expression profile in comparison with epstein-barr virus-negative carcinoma. Clin Cancer Res. 2004, 10: 1698-1705. 10.1158/1078-0432.CCR-1122-3.PubMedCrossRef
14.
Schneider BG, Gulley ML, Eagan P, Bravo JC, Mera R, Geradts J: Loss of p16/CDKN2A tumor suppressor protein in gastric adenocarcinoma is associated with Epstein-Barr virus and anatomic location in the body of the stomach. Hum Pathol. 2000, 31: 45-50. 10.1016/S0046-8177(00)80197-5.PubMedCrossRef
15.
Vo QN, Geradts J, Gulley ML, Boudreau DA, Bravo JC, Schneider BG: Epstein-Barr virus in gastric adenocarcinomas: association with ethnicity and CDKN2A promoter methylation. J Clin Pathol. 2002, 55: 669-675. 10.1136/jcp.55.9.669.PubMedPubMedCentralCrossRef
16.
Carneiro F, Oliveira C, Leite M, Seruca R: Molecular targets and biological modifiers in gastric cancer. Semin Diagn Pathol. 2008, 25: 274-287. 10.1053/j.semdp.2008.07.004.PubMedCrossRef
17.
Ushiku T, Chong JM, Uozaki H, Hino R, Chang MS, Sudo M, Rani BR, Sakuma K, Nagai H, Fukayama M: p73 gene promoter methylation in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer. 2007, 120: 60-66. 10.1002/ijc.22275.PubMedCrossRef
18.
Ferrasi AC, Pinheiro NA, Rabenhorst SH, Caballero OL, Rodrigues MA, de Carvalho F, Leite CV, Ferreira MV, Barros MA, Pardini MI: Helicobacter pylori and EBV in gastric carcinomas: methylation status and microsatellite instability. World J Gastroenterol. 2010, 16: 312-319. 10.3748/wjg.v16.i3.312.PubMedPubMedCentralCrossRef
19.
Kang GH, Lee S, Kim WH, Lee HW, Kim JC, Rhyu MG, Ro JY: Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma. Am J Pathol. 2002, 160: 787-794.PubMedPubMedCentralCrossRef
20.
Ksiaa F, Ziadi S, Amara K, Korbi S, Trimeche M: Biological significance of promoter hypermethylation of tumor-related genes in patients with gastric carcinoma. Clin Chim Acta. 2009, 404: 128-133. 10.1016/j.cca.2009.03.044.PubMedCrossRef
21.
Chong JM, Sakuma K, Sudo M, Ushiku T, Uozaki H, Shibahara J, Nagai H, Funata N, Taniguchi H, Aburatani H, Fukayama M: Global and non-random CpG-island methylation in gastric carcinoma associated with Epstein-Barr virus. Cancer Sci. 2003, 94: 76-80. 10.1111/j.1349-7006.2003.tb01355.x.PubMedCrossRef
22.
Kang GH, Lee S, Cho NY, Gandamihardja T, Long TI, Weisenberger DJ, Campan M, Laird PW: DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest. 2008, 88: 161-170. 10.1038/labinvest.3700707.PubMedCrossRef
23.
Niller HH, Wolf H, Minarovits J: Epigenetic dysregulation of the host cell genome in Epstein-Barr virus-associated neoplasia. Semin Cancer Biol. 2009, 19: 158-164. 10.1016/j.semcancer.2009.02.012.PubMedCrossRef
24.
Kusano M, Toyota M, Suzuki H, Akino K, Aoki F, Fujita M, Hosokawa M, Shinomura Y, Imai K, Tokino T: Genetic, epigenetic, and clinicopathologic features of gastric carcinomas with the CpG island methylator phenotype and an association with Epstein-Barr virus. Cancer. 2006, 106: 1467-1479. 10.1002/cncr.21789.PubMedCrossRef
25.
Fukayama M: Epstein-Barr virus and gastric carcinoma. Pathol Int. 2010, 60: 337-350. 10.1111/j.1440-1827.2010.02533.x.PubMedCrossRef
26.
Park SY, Kook MC, Kim YW, Cho NY, Kim TY, Kang GH: Mixed-type gastric cancer and its association with high-frequency CpG island hypermethylation. Virchows Arch. 2010, 456: 625-633. 10.1007/s00428-010-0916-6.PubMedCrossRef
27.
Etoh T, Kanai Y, Ushijima S, Nakagawa T, Nakanishi Y, Sasako M, Kitano S, Hirohashi S: Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. Am J Pathol. 2004, 164: 689-699.PubMedPubMedCentralCrossRef
28.
Hino R, Uozaki H, Murakami N, Ushiku T, Shinozaki A, Ishikawa S, Morikawa T, Nakaya T, Sakatani T, Takada K, Fukayama M: Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res. 2009, 69: 2766-2774. 10.1158/0008-5472.CAN-08-3070.PubMedCrossRef
29.
Sakakura C, Hagiwara A, Nakanishi M, Shimomura K, Takagi T, Yasuoka R, Fujita Y, Abe T, Ichikawa Y, Takahashi S, Ishikawa T, Nishizuka I, Morita T, Shimada H, Okazaki Y, Hayashizaki Y, Yamagishi H: Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites. Br J Cancer. 2002, 87: 1153-1161. 10.1038/sj.bjc.6600580.PubMedPubMedCentralCrossRef
30.
Tsai CL, Li HP, Lu YJ, Hsueh C, Liang Y, Chen CL, Tsao SW, Tse KP, Yu JS, Chang YS: Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signaling. Cancer Res. 2006, 66: 11668-11676. 10.1158/0008-5472.CAN-06-2194.PubMedCrossRef
31.
Tsai CN, Tsai CL, Tse KP, Chang HY, Chang YS: The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases. Proc Natl Acad Sci USA. 2002, 99: 10084-10089. 10.1073/pnas.152059399.PubMedPubMedCentralCrossRef
32.
Chan AS, Tsui WY, Chen X, Chu KM, Chan TL, Li R, So S, Yuen ST, Leung SY: Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma. Oncogene. 2003, 22: 6946-6953. 10.1038/sj.onc.1206799.PubMedCrossRef
33.
Li H, Minarovits J: Host cell-dependent expression of latent Epstein-Barr virus genomes: regulation by DNA methylation. Adv Cancer Res. 2003, 89: 133-156. full_text.PubMedCrossRef
34.
Dickerson SJ, Xing Y, Robinson AR, Seaman WT, Gruffat H, Kenney SC: Methylation-dependent binding of the epstein-barr virus BZLF1 protein to viral promoters. PLoS Pathog. 2009, 5: e1000356-10.1371/journal.ppat.1000356.PubMedPubMedCentralCrossRef
35.
Bhende PM, Seaman WT, Delecluse HJ, Kenney SC: The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Nat Genet. 2004, 36: 1099-1104. 10.1038/ng1424.PubMedCrossRef
36.
Watanabe Y, Kim HS, Castoro RJ, Chung W, Estecio MR, Kondo K, Guo Y, Ahmed SS, Toyota M, Itoh F, Suk KT, Cho MY, Shen L, Jelinek J, Issa JP: Sensitive and specific detection of early gastric cancer with DNA methylation analysis of gastric washes. Gastroenterology. 2009, 136: 2149-2158. 10.1053/j.gastro.2009.02.085.PubMedPubMedCentralCrossRef
37.
van Beek J, zur Hausen A, Kranenbarg EK, Warring RJ, Bloemena E, Craanen ME, van de Velde CJ, Middeldorp JM, Meijer CJ, van den Brule AJ: A rapid and reliable enzyme immunoassay PCR-based screening method to identify EBV-carrying gastric carcinomas. Mod Pathol. 2002, 15: 870-877. 10.1097/01.MP.0000024147.43288.B1.PubMedCrossRef
38.
zur Hausen A, Brink AA, Craanen ME, Middeldorp JM, Meijer CJ, van den Brule AJ: Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene. Cancer Research. 2000, 60: 2745-2748.PubMed
39.
Houali K, Wang X, Shimizu Y, Djennaoui D, Nicholls J, Fiorini S, Bouguermouh A, Ooka T: A new diagnostic marker for secreted Epstein-Barr virus encoded LMP1 and BARF1 oncoproteins in the serum and saliva of patients with nasopharyngeal carcinoma. Clin Cancer Res. 2007, 13: 4993-5000. 10.1158/1078-0432.CCR-06-2945.PubMedCrossRef
40.
Stevens SJ, Verkuijlen SA, Hariwiyanto B, Harijadi , Paramita DK, Fachiroh J, Adham M, Tan IB, Haryana SM, Middeldorp JM: Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings reveal high Epstein-Barr virus DNA load and carcinoma-specific viral BARF1 mRNA. Int J Cancer. 2006, 119: 608-614. 10.1002/ijc.21914.PubMedCrossRef
41.
Suzuki H, Toyota M, Kondo Y, Shinomura Y: Inflammation-related aberrant patterns of DNA methylation: detection and role in epigenetic deregulation of cancer cell transcriptome. Methods Mol Biol. 2009, 512: 55-69. full_text.PubMedCrossRef
42.
Toyota M, Suzuki H, Yamashita T, Hirata K, Imai K, Tokino T, Shinomura Y: Cancer epigenomics: implications of DNA methylation in personalized cancer therapy. Cancer Sci. 2009, 100: 787-791. 10.1111/j.1349-7006.2009.01095.x.PubMedCrossRef
43.
Yamashita S, Tsujino Y, Moriguchi K, Tatematsu M, Ushijima T: Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006, 97: 64-71. 10.1111/j.1349-7006.2006.00136.x.PubMedCrossRef
44.
Mikata R, Yokosuka O, Fukai K, Imazeki F, Arai M, Tada M, Kurihara T, Zhang K, Kanda T, Saisho H: Analysis of genes upregulated by the demethylating agent 5-aza-2'-deoxycytidine in gastric cancer cell lines. Int J Cancer. 2006, 119: 1616-1622. 10.1002/ijc.21968.PubMedCrossRef
45.
Jung EJ, Lee YM, Lee BL, Chang MS, Kim WH: Lytic induction and apoptosis of Epstein-Barr virus-associated gastric cancer cell line with epigenetic modifiers and ganciclovir. Cancer Lett. 2007, 247: 77-83. 10.1016/j.canlet.2006.03.022.PubMedCrossRef
46.
Mitsuno M, Kitajima Y, Ide T, Ohtaka K, Tanaka M, Satoh S, Miyazaki K: Aberrant methylation of p16 predicts candidates for 5-fluorouracil-based adjuvant therapy in gastric cancer patients. J Gastroenterol. 2007, 42: 866-873. 10.1007/s00535-007-2113-1.PubMedCrossRef
47.
Feng WH, Westphal E, Mauser A, Raab-Traub N, Gulley ML, Busson P, Kenney SC: Use of adenovirus vectors expressing Epstein-Barr virus (EBV) immediate-early protein BZLF1 or BRLF1 to treat EBV-positive tumors. J Virol. 2002, 76: 10951-10959. 10.1128/JVI.76.21.10951-10959.2002.PubMedPubMedCentralCrossRef
48.
Kassis J, Maeda A, Teramoto N, Takada K, Wu C, Klein G, Wells A: EBV-expressing AGS gastric carcinoma cell sublines present increased motility and invasiveness. Int J Cancer. 2002, 99: 644-651. 10.1002/ijc.10382.PubMedCrossRef
49.
Kang GH, Lee S, Kim JS, Jung HY: Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis. Lab Invest. 2003, 83: 635-641.PubMedCrossRef
50.
Varis A, Zaika A, Puolakkainen P, Nagy B, Madrigal I, Kokkola A, Vayrynen A, Karkkainen P, Moskaluk C, El-Rifai W, Knuutila S: Coamplified and overexpressed genes at ERBB2 locus in gastric cancer. Int J Cancer. 2004, 109: 548-553. 10.1002/ijc.20001.PubMedCrossRef
51.
Hong GK, Delecluse HJ, Gruffat H, Morrison TE, Feng WH, Sergeant A, Kenney SC: The BRRF1 early gene of Epstein-Barr virus encodes a transcription factor that enhances induction of lytic infection by BRLF1. J Virol. 2004, 78: 4983-4992. 10.1128/JVI.78.10.4983-4992.2004.PubMedPubMedCentralCrossRef
52.
Ryan JL, Fan H, Glaser SL, Schichman SA, Raab-Traub N, Gulley ML: Epstein-Barr virus quantitation by real-time PCR targeting multiple gene segments: a novel approach to screen for the virus in paraffin-embedded tissue and plasma. J Mol Diagn. 2004, 6: 378-385.PubMedPubMedCentralCrossRef
53.
Ling PD, Vilchez RA, Keitel WA, Poston DG, Peng RS, White ZS, Visnegarwala F, Lewis DE, Butel JS: Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy. Clin Infect Dis. 2003, 37: 1244-1249. 10.1086/378808.PubMedCrossRef
54.
Hamai Y, Oue N, Mitani Y, Nakayama H, Ito R, Matsusaki K, Yoshida K, Toge T, Yasui W: DNA hypermethylation and histone hypoacetylation of the HLTF gene are associated with reduced expression in gastric carcinoma. Cancer Sci. 2003, 94: 692-698. 10.1111/j.1349-7006.2003.tb01504.x.PubMedCrossRef
55.
Katoh M: Trefoil factors and human gastric cancer. Int J Mol Med. 2003, 12: 3-9.PubMed
56.
Leung WK, Yu J, Bai AH, Chan MW, Chan KK, To KF, Chan FK, Ng EK, Chung SC, Sung JJ: Inactivation of helicase-like transcription factor by promoter hypermethylation in human gastric cancer. Mol Carcinog. 2003, 37: 91-97. 10.1002/mc.10124.PubMedCrossRef
57.
Liu SJ, Cai ZW, Liu YJ, Dong MY, Sun LQ, HU GF, Wei YY, Lao WD: Role of nucleostemin in growth regulation of gastric cancer, liver cancer, and other malignancies. World J Gastroenterol. 2004, 10: 1246-1249.PubMedPubMedCentral
58.
Meyer NP, Johansen LM, Tae HJ, Budde PP, Williams KL, Taparowsky EJ: Genomic organization of human B-ATF, a target for regulation by EBV and HTLV-1. Mamm Genome. 1998, 9: 849-852. 10.1007/s003359900881.PubMedCrossRef
59.
Ren JL, Luo JY, Lu YP, Wang L, Shi HX: Relationship between trefoil factor 1 expression and gastric mucosa injuries and gastric cancer. World J Gastroenterol. 2005, 11: 2674-2677.PubMedPubMedCentralCrossRef
60.
Rivenbark AG, Jones WD, Coleman WB: DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Lab Invest. 2006, 86: 1233-1242. 10.1038/labinvest.3700485.PubMedCrossRef
61.
Rivenbark AG, Jones WD, Risher JD, Coleman WB: DNA methylation-dependent epigenetic regulation of gene expression in MCF-7 breast cancer cells. Epigenetics. 2006, 1: 32-44. 10.4161/epi.1.1.2358.PubMedCrossRef
62.
Gardiner-Garden M, Frommer M: CpG islands in vertebrate genomes. J Mol Biol. 1987, 196: 261-282. 10.1016/0022-2836(87)90689-9.PubMedCrossRef
63.
Akiba S, Koriyama C, Herrera-Goepfert R, Eizuru Y: Epstein-Barr virus associated gastric carcinoma: epidemiological and clinicopathological features. Cancer Sci. 2008, 99: 195-201. 10.1111/j.1349-7006.2007.00674.x.PubMedCrossRef
64.
Kida Y, Miyauchi K, Takano Y: Gastric adenocarcinoma with differentiation to sarcomatous components associated with monoclonal Epstein-Barr virus infection and LMP-1 expression. Virchows Arch A Pathol Anat Histopathol. 1993, 423: 383-387. 10.1007/BF01607151.PubMedCrossRef
65.
Feng WH, Kraus RJ, Dickerson SJ, Lim HJ, Jones RJ, Yu X, Mertz JE, Kenney SC: ZEB1 and c-Jun levels contribute to the establishment of highly lytic Epstein-Barr virus infection in gastric AGS cells. J Virol. 2007, 81: 10113-10122. 10.1128/JVI.00692-07.PubMedPubMedCentralCrossRef
66.
Huang J, Liao G, Chen H, Wu FY, Hutt-Fletcher L, Hayward GS, Hayward SD: Contribution of C/EBP proteins to Epstein-Barr virus lytic gene expression and replication in epithelial cells. J Virol. 2006, 80: 1098-1109. 10.1128/JVI.80.3.1098-1109.2006.PubMedPubMedCentralCrossRef
67.
Chen JN, Ding YG, Feng ZY, Li HG, He D, Du H, Wu B, Shao CK: Association of distinctive Epstein-Barr virus variants with gastric carcinoma in Guangzhou, southern China. J Med Virol. 82: 658-667. 10.1002/jmv.21731.
68.
Oh ST, Seo JS, Moon UY, Kang KH, Shin DJ, Yoon SK, Kim WH, Park JG, Lee SK: A naturally derived gastric cancer cell line shows latency I Epstein-Barr virus infection closely resembling EBV-associated gastric cancer. Virology. 2004, 320: 330-336. 10.1016/j.virol.2003.12.005.PubMedCrossRef
69.
zur Hausen A, Brink AA, Craanen ME, Middeldorp JM, Meijer CJ, van den Brule AJ: Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene. Cancer Res. 2000, 60: 2745-2748.PubMed
70.
Sheu LF, Chen A, Wei YH, Ho KC, Cheng JY, Meng CL, Lee WH: Epstein-Barr virus LMP1 modulates the malignant potential of gastric carcinoma cells involving apoptosis. Am J Pathol. 1998, 152: 63-74.PubMedPubMedCentral
71.
Luo B, Wang Y, Wang XF, Gao Y, Huang BH, Zhao P: Correlation of Epstein-Barr virus and its encoded proteins with Helicobacter pylori and expression of c-met and c-myc in gastric carcinoma. World J Gastroenterol. 2006, 12: 1842-1848.PubMedPubMedCentral
72.
Luo B, Wang Y, Wang XF, Liang H, Yan LP, Huang BH, Zhao P: Expression of Epstein-Barr virus genes in EBV-associated gastric carcinomas. World J Gastroenterol. 2005, 11: 629-633.PubMedPubMedCentralCrossRef
73.
Tsurumi T, Fujita M, Kudoh A: Latent and lytic Epstein-Barr virus replication strategies. Rev Med Virol. 2005, 15: 3-15. 10.1002/rmv.441.PubMedCrossRef
74.
Holley-Guthrie EA, Seaman WT, Bhende P, Merchant JL, Kenney SC: The Epstein-Barr virus protein BMRF1 activates gastrin transcription. J Virol. 2005, 79: 745-755. 10.1128/JVI.79.2.745-755.2005.PubMedPubMedCentralCrossRef
75.
Burkitt MD, Varro A, Pritchard DM: Importance of gastrin in the pathogenesis and treatment of gastric tumors. World J Gastroenterol. 2009, 15: 1-16. 10.3748/wjg.15.1.PubMedPubMedCentralCrossRef
76.
Khan ZE, Wang TC, Cui G, Chi AL, Dimaline R: Transcriptional regulation of the human trefoil factor, TFF1, by gastrin. Gastroenterology. 2003, 125: 510-521. 10.1016/S0016-5085(03)00908-9.PubMedCrossRef
77.
Carvalho R, Kayademir T, Soares P, Canedo P, Sousa S, Oliveira C, Leistenschneider P, Seruca R, Gott P, Blin N, Carneiro F, Machado JC: Loss of heterozygosity and promoter methylation, but not mutation, may underlie loss of TFF1 in gastric carcinoma. Lab Invest. 2002, 82: 1319-1326.PubMedCrossRef
78.
Noetzel E, Veeck J, Niederacher D, Galm O, Horn F, Hartmann A, Knuchel R, Dahl E: Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer. BMC Cancer. 2008, 8: 154-10.1186/1471-2407-8-154.PubMedPubMedCentralCrossRef
79.
Iglesias D, Nejda N, Azcoita MM, Schwartz S, Gonzalez-Aguilera JJ, Fernandez-Peralta AM: Effect of COX2 -765G > C and c.3618A > G polymorphisms on the risk and survival of sporadic colorectal cancer. Cancer Causes Control. 2009, 20: 1421-1429. 10.1007/s10552-009-9368-1.PubMedCrossRef
80.
Okano H, Shinohara H, Miyamoto A, Takaori K, Tanigawa N: Concomitant overexpression of cyclooxygenase-2 in HER-2-positive on Smad4-reduced human gastric carcinomas is associated with a poor patient outcome. Clin Cancer Res. 2004, 10: 6938-6945. 10.1158/1078-0432.CCR-0731-03.PubMedCrossRef
81.
Ono HA, Davydova JG, Adachi Y, Takayama K, Barker SD, Reynolds PN, Krasnykh VN, Kunisaki C, Shimada H, Curiel DT, Yamamoto M: Promoter-controlled infectivity-enhanced conditionally replicative adenoviral vectors for the treatment of gastric cancer. J Gastroenterol. 2005, 40: 31-42. 10.1007/s00535-004-1490-y.PubMedCrossRef
82.
Fukuhara K, Osugi H, Takada N, Takemura M, Lee S, Morimura K, Taguchi S, Kaneko M, Tanaka Y, Fujiwara Y, Nishizawa S, Fukushima S, Kinoshita H: Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy. Hepatogastroenterology. 2004, 51: 1515-1518.PubMed
83.
Chen XL, Su BS, Sun RQ, Zhang J, Wang YL: Relationship between expression and distribution of cyclooxygenase-2 and bcl-2 in human gastric adenocarcinoma. World J Gastroenterol. 2005, 11: 1228-1231.PubMedPubMedCentralCrossRef
84.
Koga T, Shibahara K, Kabashima A, Sumiyoshi Y, Kimura Y, Takahashi I, Kakeji Y, Maehara Y: Overexpression of cyclooxygenase-2 and tumor angiogenesis in human gastric cancer. Hepatogastroenterology. 2004, 51: 1626-1630.PubMed
85.
Jang TJ: Expression of proteins related to prostaglandin E2 biosynthesis is increased in human gastric cancer and during gastric carcinogenesis. Virchows Arch. 2004, 445: 564-571. 10.1007/s00428-004-1104-3.PubMedCrossRef
86.
Nardone G, Rocco A, Vaira D, Staibano S, Budillon A, Tatangelo F, Sciulli MG, Perna F, Salvatore G, Di Benedetto M, De Rosa G, Patrignani P: Expression of COX-2, mPGE-synthase1, MDR-1 (P-gp), and Bcl-xL: a molecular pathway of H pylori-related gastric carcinogenesis. J Pathol. 2004, 202: 305-312. 10.1002/path.1512.PubMedCrossRef
87.
Sun WH, Yu Q, Shen H, Ou XL, Cao DZ, Yu T, Qian C, Zhu F, Sun YL, Fu XL, Su H: Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis. World J Gastroenterol. 2004, 10: 2809-2813.PubMedPubMedCentralCrossRef
88.
Barry EL, Sansbury LB, Grau MV, Ali IU, Tsang S, Munroe DJ, Ahnen DJ, Sandler RS, Saibil F, Gui J, Bresalier RS, McKeown-Eyssen GE, Burke C, Baron JA: Cyclooxygenase-2 polymorphisms, aspirin treatment, and risk for colorectal adenoma recurrence--data from a randomized clinical trial. Cancer Epidemiol Biomarkers Prev. 2009, 18: 2726-2733. 10.1158/1055-9965.EPI-09-0363.PubMedPubMedCentralCrossRef
89.
Song SH, Jong HS, Choi HH, Inoue H, Tanabe T, Kim NK, Bang YJ: Transcriptional silencing of Cyclooxygenase-2 by hyper-methylation of the 5' CpG island in human gastric carcinoma cells. Cancer Res. 2001, 61: 4628-4635.PubMed
90.
de Maat MF, van de Velde CJ, Umetani N, de Heer P, Putter H, van Hoesel AQ, Meijer GA, van Grieken NC, Kuppen PJ, Bilchik AJ, Tollenaar RA, Hoon DS: Epigenetic silencing of cyclooxygenase-2 affects clinical outcome in gastric cancer. J Clin Oncol. 2007, 25: 4887-4894. 10.1200/JCO.2006.09.8921.PubMedCrossRef
91.
Epplein M, Nomura AM, Wilkens LR, Henderson BE, Kolonel LN: Nonsteroidal antiinflammatory drugs and risk of gastric adenocarcinoma: the multiethnic cohort study. Am J Epidemiol. 2009, 170: 507-514. 10.1093/aje/kwp162.PubMedPubMedCentralCrossRef
92.
Park ES, Do IG, Park CK, Kang WK, Noh JH, Sohn TS, Kim S, Kim MJ, Kim KM: Cyclooxygenase-2 is an independent prognostic factor in gastric carcinoma patients receiving adjuvant chemotherapy and is not associated with EBV infection. Clin Cancer Res. 2009, 15: 291-298. 10.1158/1078-0432.CCR-08-0848.PubMedCrossRef
93.
Chen W, Wang L, Ke Q, Jin G, Tan Y, Zhou Y, Hu Z, Ma H, Wang J, Hua Z, Ding W, Shen J, Xu Y, Shen H: The role of IGFBP3 functional polymorphisms in the risk of gastric cancer in a high-risk Chinese population. Eur J Cancer Prev. 2008, 17: 82-87. 10.1097/CEJ.0b013e32809b4cff.PubMedCrossRef
94.
Pereira C, Medeiros RM, Dinis-Ribeiro MJ: Cyclooxygenase polymorphisms in gastric and colorectal carcinogenesis: are conclusive results available?. Eur J Gastroenterol Hepatol. 2009, 21: 76-91. 10.1097/MEG.0b013e32830ce7ba.PubMedCrossRef
95.
Jeng YM, Wang TH, Lu SH, Yuan RH, Hsu HC: Prognostic significance of insulin-like growth factor II mRNA-binding protein 3 expression in gastric adenocarcinoma. Br J Surg. 2009, 96: 66-73. 10.1002/bjs.6438.PubMedCrossRef
96.
Tomii K, Tsukuda K, Toyooka S, Dote H, Hanafusa T, Asano H, Naitou M, Doihara H, Kisimoto T, Katayama H, Pass HI, Date H, Shimizu N: Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers. Int J Cancer. 2007, 120: 566-573. 10.1002/ijc.22341.PubMedCrossRef
97.
Lee DY, Yi HK, Hwang PH, Oh Y: Enhanced expression of insulin-like growth factor binding protein-3 sensitizes the growth inhibitory effect of anticancer drugs in gastric cancer cells. Biochem Biophys Res Commun. 2002, 294: 480-486. 10.1016/S0006-291X(02)00491-6.PubMedCrossRef
98.
Garcia-Manero G: Demethylating agents in myeloid malignancies. Curr Opin Oncol. 2008, 20: 705-710. 10.1097/CCO.0b013e328313699c.PubMedCrossRef
Metadata
Title
Epstein-Barr virus-specific methylation of human genes in gastric cancer cells
Authors
Julie L Ryan
Richard J Jones
Shannon C Kenney
Ashley G Rivenbark
Weihua Tang
Elizabeth RW Knight
William B Coleman
Margaret L Gulley
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Infectious Agents and Cancer / Issue 1/2010
Electronic ISSN: 1750-9378
DOI
https://doi.org/10.1186/1750-9378-5-27

Other articles of this Issue 1/2010

Infectious Agents and Cancer 1/2010 Go to the issue

Research article

Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30

Research article

Risk of classic Kaposi sarcoma with exposures to plants and soils in Sicily

Review

HPV - immune response to infection and vaccination

Short report

Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma

Methodology

Ultrasensitive quantitation of human papillomavirus type 16 E6 oncogene sequences by nested real time PCR

Short report

HLA polymorphisms and detection of kaposi sarcoma-associated herpesvirus DNA in saliva and peripheral blood among children and their mothers in the uganda sickle cell anemia KSHV Study
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits