Skip to main content
SpringerLink
Log in

Helicobacter pylori strain-specific modulation of gastric mucosal cellular turnover: implications for carcinogenesis

  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Helicobacter pylori colonization induces inflammation in essentially all hosts, a persistent process that increases the risk of developing distal gastric adenocarcinoma. However, only a small percentage of persons carryingH. pylori develop neoplasia; enhanced risk may be related to differences in expression of specific bacterial products, differences in the host response to the bacteria, or the interaction between host and microbe.H. pylori strains that have thecag pathogenicity island are associated with further increased risk for developing distal gastric cancer; however, host responses toH. pylori, such as altered epithelial cell proliferation and apoptosis, also may be important in lowering the threshold for carcinogenesis.H. pylori cag+ strains selectively enhance proliferation and attenuate apoptosis in human mucosa compared tocag− strains. However,cag+ strains also induce more severe gastritis, suggesting that host inflammatory mediators such as cytokines, prostaglandins, and hormones may modulateH. pylori-induced alterations in cellular turnover. In the Mongolian gerbil model of gastric carcinogenesis, apoptosis increases early and transiently followingH. pylori infection, but scores progressively decline despite worsening gastric inflammation. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growth inH. pylori-colonized mucosa may be mediated by gastrin-dependent mechanisms. An emerging model invoked by these data is one in whichH. pylori cag+ strains, in conjunction with host mediators, enhance gastric epithelial cell proliferation but not apoptosis in vivo. The combination of increased proliferation without a concordant increase in apoptosis may therefore contribute to the heightened retention of mutagenized cells, which over decades may increase the subsequent risk for gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1:1311–5.

    Article  PubMed  CAS  Google Scholar 

  2. Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ. Attempt to fulfil Koch’s postulates for pyloricCampylobacter. Med J Aust 1985;142:436–9.

    PubMed  CAS  Google Scholar 

  3. Morris A, Nicholson G. Ingestion ofCampylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol 1987;82:192–9.

    PubMed  CAS  Google Scholar 

  4. Dooley CP, McKenna D, Humphreys H, Bourke S, Keane CT, Sweeney E, et al. Histological gastritis in duodenal ulcer: relationship toCampylobacter pylori and effect of ulcer therapy. Am J Gastroenterol 1988;83:278–82.

    PubMed  CAS  Google Scholar 

  5. Taylor DN, Blaser MJ. The epidemiology ofHelicobacter pylori infection. Epidemiol Rev 1991;13:42–59.

    PubMed  CAS  Google Scholar 

  6. Langenberg W, Rauws EA, Widjojokusumo A, Tytgat GN, Zanen HC. Identification ofCampylobacter pyloridis isolates by restriction endonuclease DNA analysis. J Clin Microbiol 1986; 24:414–17.

    PubMed  CAS  Google Scholar 

  7. Rauws EA, Langenberg W, Houthoff HJ, Zanen HC, Tytgat GN.Campylobacter pyloridis-associated chronic active antral gastritis: a prospective study of its prevalence and the effects of antibacterial and antiulcer treatment. Gastroenterology 1988; 94:33–40.

    PubMed  CAS  Google Scholar 

  8. Dooley CP, Cohen H, Fitzgibbons PL, Bauer M, Appleman MD, Perez-Perez GI, et al. Prevalence ofHelicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med 1989;321:1562–6.

    PubMed  CAS  Google Scholar 

  9. Karnes WE Jr, Samloff IM, Siurala M, Kekki M, Sipponen P, Kim SW, et al. Positive serum antibody and negative tissue staining forHelicobacter pylori in subjects with atrophic body gastritis. Gastroenterology 1991;101:167–74.

    PubMed  Google Scholar 

  10. Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ.Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 1991;325:1132–6.

    PubMed  CAS  Google Scholar 

  11. Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al.Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 1991;325:1127–31.

    PubMed  CAS  Google Scholar 

  12. Talley NJ, Zinsmeister AR, Weaver A, DiMagno EP, Carpenter HA, Perez-Perez GI, et al. Gastric adenocarcinoma andHelicobacter pylori infection. J Natl Cancer Inst 1991;83:1734–9.

    Article  PubMed  CAS  Google Scholar 

  13. Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N, et al. Association between infection withHelicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ 1991;302:1302–5.

    PubMed  CAS  Google Scholar 

  14. Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship betweenHelicobacter pylori seropositivity and gastric cancer. Gastroenterology 1998;114:1169–79.

    Article  PubMed  CAS  Google Scholar 

  15. Correa P.Helicobacter pylori and gastric cancer: state of the art. Cancer Epidemiol Biomarkers Prev 1996;5:477–81.

    PubMed  CAS  Google Scholar 

  16. Vicari JJ, Peek RM, Falk GW, Goldblum JR, Easley KA, Schnell J, et al. The seroprevalence ofcagA-positiveHelicobacter pylori strains in the spectrum of gastroesophageal reflux disease. Gastroenterology 1998;115:50–7.

    Article  PubMed  CAS  Google Scholar 

  17. Chow WH, Blaser MJ, Blot WJ, Gammon MD, Vaughan TL, Risch HA, et al. An inverse relation betweencagA + strains ofHelicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer Res 1998;58:588–90.

    PubMed  CAS  Google Scholar 

  18. Peek RM Jr, Vaezi MF, Falk GW, Goldblum JR, Perez-Perez GI, Richter JE, et al. Role ofHelicobacter pylori cagA(+) strains and specific host immune responses on the development of premalignant and malignant lesions in the gastric cardia. Int J Cancer 1999;82:520–4.

    Article  PubMed  Google Scholar 

  19. Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, et al.cag, a pathogenicity island ofHelicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA 1996;93:14648–53.

    Article  PubMed  CAS  Google Scholar 

  20. Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE, Reece CA, et al. Analyses of thecag pathogenicity island ofHelicobacter pylori. Mol Microbiol 1998;28:37–53.

    Article  PubMed  CAS  Google Scholar 

  21. Odenbreit S, Puls J, Sedlmaier B, Gerland E, Fischer W, Haas R. Translocation ofHelicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 2000;287:1497–500.

    Article  PubMed  CAS  Google Scholar 

  22. Stein M, Rappuoli R, Covacci A. Tyrosine phosphorylation of theHelicobacter pylori CagA antigen aftercag-driven host cell translocation. Proc Natl Acad Sci USA 2000;97:1263–8.

    Article  PubMed  CAS  Google Scholar 

  23. Asahi M, Azuma T, Ito S, Ito Y, Suto H, Nagai Y, et al.Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med 2000;191:593–602.

    Article  PubMed  CAS  Google Scholar 

  24. Keates S, Keates AC, Warny M, Peek RM Jr, Murray PG, Kelly CP. Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells bycag + andcag − Helicobacter pylori. J Immunol 1999;163:5552–9.

    PubMed  CAS  Google Scholar 

  25. Naumann M, Wessler S, Bartsch C, Wieland B, Covacci A, Haas R, et al. Activation of activator protein 1 and stress response kinases in epithelial cells colonized byHelicobacter pylori encoding thecag pathogenicity island. J Biol Chem 1999;274:31655–62.

    Article  PubMed  CAS  Google Scholar 

  26. Meyer-Ter-Vehn T, Covacci A, Kist M, Pahl HL.Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-jun. J Biol Chem 2000;275:16064–72.

    Article  PubMed  CAS  Google Scholar 

  27. Keates S, Hitti YS, Upton M, Kelly CP.Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells. Gastroenterology 1997;113:1099–109.

    Article  PubMed  CAS  Google Scholar 

  28. Aihara M, Tsuchimoto D, Takizawa H, Azuma A, Wakebe H, Ohmoto Y, et al. Mechanisms involved inHelicobacter pyloriinduced interleukin-8 production by a gastric cancer cell line, MKN45. Infect Immun 1997;65:3218–24.

    PubMed  CAS  Google Scholar 

  29. Sharma SA, Tummuru MK, Blaser MJ, Kerr LD. Activation of IL-8 gene expression byHelicobacter pylori is regulated by transcription factor nuclear factor-kappa B in gastric epithelial cells. J Immunol 1998;160:2401–7.

    PubMed  CAS  Google Scholar 

  30. Glocker E, Lange C, Covacci A, Bereswill S, Kist M, Pahl HL. Proteins encoded by thecag pathogencity island ofHelicobacter pylori are required for NF-kappa B activation. Infect Immun 1998;66:2346–8.

    PubMed  CAS  Google Scholar 

  31. Tummuru MK, Sharma SA, Blaser MJ.Helicobacter pylori picB, a homologue of theBordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells. Mol Microbiol 1995;18:867–76.

    Article  PubMed  CAS  Google Scholar 

  32. Peek RM Jr, Blaser MJ, Mays DJ, Forsyth MH, Cover TL, Song SY, et al.Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle. Cancer Res 1999;59:6124–31.

    PubMed  CAS  Google Scholar 

  33. Peek RM Jr, Miller GG, Tham KT, Perez-Perez GI, Cover TL, Atherton JC, et al. Detection ofHelicobacter pylori gene expression in human gastric mucosa. J Clin Microbiol 1995;33:28–32.

    PubMed  CAS  Google Scholar 

  34. Peek RM Jr, Miller GG, Tham KT, Perez-Perez GI, Zhao X, Atherton JC, et al. Heightened inflammatory response and cytokine expression in vivo tocagA + Helicobacter pylori strains. Lab Invest 1995;73:760–70.

    PubMed  CAS  Google Scholar 

  35. Cover TL, Dooley CP, Blaser MJ. Characterization of and human serologic response to proteins inHelicobacter pylori broth culture supernatants with vacuolizing cytotoxin activity. Infect Immun 1990;58:603–10.

    PubMed  CAS  Google Scholar 

  36. Crabtree JE, Taylor JD, Wyatt JI, Heatley RV, Shallcross TM, Tompkins DS, et al. Mucosal IgA recognition ofHelicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology. Lancet 1991;338:332–5.

    Article  PubMed  CAS  Google Scholar 

  37. Kuipers EJ, Perez-Perez GI, Meuwissen SG, Blaser MJ.Helicobacter pylori and atrophic gastritis: importance of thecagA status. J Natl Cancer Inst 1995;87:1777–80.

    Article  PubMed  CAS  Google Scholar 

  38. Crabtree JE, Wyatt JI, Sobala GM, Miller G, Tompkins DS, Primrose JN, et al. Systemic and mucosal humoral responses toHelicobacter pylori in gastric cancer. Gut 1993;34:1339–43.

    Article  PubMed  CAS  Google Scholar 

  39. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, et al. Infection withHelicobacter pylori strains possessingcagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 1995;55:2111–5.

    PubMed  CAS  Google Scholar 

  40. Parsonnet J, Friedman GD, Orentreich N, Vogelman H. Risk for gastric cancer in people with CagA positive or CagA negativeHelicobacter pylori infection. Gut 1997;40:297–301.

    PubMed  CAS  Google Scholar 

  41. Rudi J, Kolb C, Maiwald M, Zuna I, von Herbay A, Galle PR, et al. Serum antibodies againstHelicobacter pylori proteins VacA and CagA are associated with increased risk for grastric adenocarcinoma. Dig Dis Sci 1997;42:1652–9.

    Article  PubMed  CAS  Google Scholar 

  42. Queiroz DM, Mendes EN, Rocha GA, Oliveira AM, Oliveira CA, Magalhaes PP, et al.cagA-positiveHelicobacter pylori and risk for developing gastric carcinoma in Brazil. Int J Cancer 1998;78:135–9.

    Article  PubMed  CAS  Google Scholar 

  43. Torres J, Perez-Perez GI, Leal-Herrera Y, Munoz O. Infection with CagA+Helicobacter pylori strains as a possible predictor of risk in the development of gastric adenocarcinoma in Mexico. Int J Cancer 1998;78:298–300.

    Article  PubMed  CAS  Google Scholar 

  44. Vorobjova T, Nilsson I, Kull K, Maaroos HI, Covacci A, Wadstrom T, et al. CagA protein seropositivity in a random sample of adult population and gastric cancer patients in Estonia. Eur J Gastroenterol Hepatol 1998;10:41–6.

    Article  PubMed  CAS  Google Scholar 

  45. Shimoyama T, Fukuda S, Tanaka M, Mikami T, Munakata A, Crabtree JE. CagA seropositivity associated with development of gastric cancer in a Japanese population. J Clin Pathol 1998;51:225–8.

    Article  PubMed  CAS  Google Scholar 

  46. Leunk RD, Johnson PT, David BC, Kraft WG, Morgan DR. Cytotoxic activity in broth-culture filtrates ofCampylobacter pylori. J Med Microbiol 1988;26:93–9.

    PubMed  CAS  Google Scholar 

  47. Figura N, Guglielmetti P, Rossolini A, Barberi A, Cusi G, Musmanno RA, et al. Cytotoxin production byCampylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only. J Clin Microbiol 1989;27:225–6.

    PubMed  CAS  Google Scholar 

  48. Cover TL, Blaser MJ. Purification and characterization of the vacuolating toxin fromHelicobacter pylori. J Biol Chem 1992;267:10570–5.

    PubMed  CAS  Google Scholar 

  49. Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles ofHelicobacter pylori: association of specificvacA types with cytotoxin production and peptic ulceration. J Biol Chem 1995;270:17771–7.

    Article  PubMed  CAS  Google Scholar 

  50. Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ. Clinical and pathological importance of heterogeneity invacA, the vacuolating cytotoxin gene ofHelicobacter pylori. Gastroenterology 1997;112:92–9.

    Article  PubMed  CAS  Google Scholar 

  51. Peek RM Jr, Thompson SA, Donahue JP, Tham KT, Atherton JC, Blaser MJ, et al. Adherence to gastric epithelial cells induces expression of aHelicobacter pylori gene,iceA, that is associated with clinical outcome. Proc Assoc Am Physicians 1998;110:531–44.

    PubMed  CAS  Google Scholar 

  52. Van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, et al. Clinical relevance of thecagA, vacA, andiceA status ofHelicobacter pylori. Gastroenterology 1998;115:58–66.

    Article  PubMed  Google Scholar 

  53. Nishiya D, Shimoyama T, Fukuda S, Yoshimura T, Tanaka M, Munakata A. Evaluation of the clinical relevance of theiceA1 gene in patients withHelicobacter pylori infection in Japan. Scand J Gastroenterol 2000;35:36–9.

    Article  PubMed  CAS  Google Scholar 

  54. Forman D.Helicobacter pylori infection: a novel risk factor in the etiology of gastric cancer. J Natl Cancer Inst 1991;83:1702–3.

    Article  PubMed  CAS  Google Scholar 

  55. Fraser AG, Sim R, Sankey EA, Dhillon AP, Pounder RE. Effect of eradication ofHelicobacter pylori on gastric epithelial cell proliferation. Aliment Pharmacol Ther 1994;8:167–73.

    Article  PubMed  CAS  Google Scholar 

  56. Bechi P, Balzi M, Becciolini A, Maugeri A, Raggi CC, Amorosi A, et al.Helicobacter pylori and cell proliferation of the gastric mucosa: possible implications for gastric carcinogenesis. Am J Gastroenterol 1996;91:271–6.

    PubMed  CAS  Google Scholar 

  57. Peek RM Jr, Moss SF, Tham KT, Perez-Perez GI, Wang S, Miller GG, et al.Helicobacter pylori cagA + strains and dissociation of gastric epithelial cell proliferation from apoptosis. J Natl Cancer Inst 1997;89:863–8.

    Article  PubMed  CAS  Google Scholar 

  58. Chow KW, Bank S, Ahn J, Roberts J, Blumstein M, Kranz V.Helicobacter pylori infection does not increase gastric antrum mucosal cell proliferation. Am J Gastroenterol 1995;90:64–6.

    PubMed  CAS  Google Scholar 

  59. Moss SF, Calam J, Agarwal B, Wang S, Holt PR. Induction of gastric epithelial apoptosis byHelicobacter pylori. Gut 1996;38:498–501.

    Article  PubMed  CAS  Google Scholar 

  60. Vaux DL, Strasser A. The molecular biology of apoptosis. Proc Natl Acad Sci USA 1996;93:2239–44.

    Article  PubMed  CAS  Google Scholar 

  61. Mannick EE, Bravo LE, Zarama G, Realpe JL, Zhang XJ, Ruiz B, et al. Inducible nitric oxide synthase, nitrotyrosine, and apoptosis inHelicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res 1996;56:3238–43.

    PubMed  CAS  Google Scholar 

  62. Jones NL, Shannon PT, Cutz E, Yeger H, Sherman PM. Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history ofHelicobacter pylori infection. Am J Pathol 1997;151:1695–1703.

    PubMed  CAS  Google Scholar 

  63. Zhu GH, Yang XL, Lai KC, Ching CK, Wong BC, Yuen ST, et al. Nonsteroidal antiinflammatory drugs could reverseHelicobacter pylori-induced apoptosis and proliferation in gastric epithelial cells. Dig Dis Sci 1998;43:1957–63.

    Article  PubMed  CAS  Google Scholar 

  64. Rokkas T, Ladas S, Liatsos C, Petridou E, Papatheodorou G, Theocharis S, et al. Relationship ofHelicobacter pylori CagA status to gastric cell proliferation and apoptosis. Dig Dis Sci 1999;44:487–93.

    Article  PubMed  CAS  Google Scholar 

  65. Moss SF, Scholes JV, Holt PR. Abnormalities of epithelial apoptosis in multistep colorectal neoplasia demonstrated by terminal deoxyuridine nick end labeling. Dig Dis Sci 1996;41:2238–47.

    Article  PubMed  CAS  Google Scholar 

  66. Bedi A, Pasricha PJ, Akhtar AJ, Barber JP, Bedi GC, Giardiello FM, et al. Inhibition of apoptosis during development of colorectal cancer. Cancer Res 1995;55:1811–16.

    PubMed  CAS  Google Scholar 

  67. Matsumoto S, Washizuka Y, Matsumoto Y, Tawara S, Ikeda F, Yokota Y, et al. Induction of ulceration and severe gastritis in Mongolian gerbil byHelicobacter pylori infection. J Med Microbiol 1997;46:391–7.

    PubMed  CAS  Google Scholar 

  68. Hirayama F, Takagi S, Yokoyama Y, Iwao E, Ikeda Y. Establishment of gastricHelicobacter pylori infection in Mongolian gerbils. J Gastroenterol 1996;31(suppl 9):24–8.

    PubMed  Google Scholar 

  69. Wirth HP, Beins MH, Yang M, Tham KT, Blaser MJ. Experimental infection of Mongolian gerbils with wild-type and mutantHelicobacter pylori strains. Infect Immun 1998;66:4856–66.

    PubMed  CAS  Google Scholar 

  70. Ikeno T, Ota H, Sugiyama A, Ishida K, Katsuyama T, Genta RM, et al.Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils. Am J Pathol 1999;154:951–60.

    PubMed  CAS  Google Scholar 

  71. Honda S, Fujioka T, Tokieda M, Gotoh T, Nishizono A, Nasu M. Gastric ulcer, atrophie gastritis, and intestinal metaplasia caused byHelicobacter pylori infection in Mongolian gerbils. Scand J Gastroenterol 1998;33:454–60.

    Article  PubMed  CAS  Google Scholar 

  72. Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M.Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterology 1998;115:642–8.

    Article  PubMed  CAS  Google Scholar 

  73. Honda S, Fujioka T, Tokieda M, Satoh R, Nishizono A, Nasu M. Development ofHelicobacter pylori-induced gastric carcinoma in Mongolian gerbils. Cancer Res 1998;58:4255–9.

    PubMed  CAS  Google Scholar 

  74. McColl KE, el-Omar E.Helicobacter pylori and disturbance of gastric function associated with duodenal ulcer disease and gastric cancer. Scand J Gastroenterol Suppl 1996;215:32–7.

    Article  PubMed  CAS  Google Scholar 

  75. Hocker M, Henihan RJ, Rosewicz S, Riecken EO, Zhang Z, Koh TJ, et al. Gastrin and phorbol 12-myristate 13-acetate regulate the human histidine decarboxylase promoter through Rafdependent activation of extracellular signal-regulated kinaserelated signaling pathways in gastric cancer cells. J Biol Chem 1997;272:27015–24.

    Article  PubMed  CAS  Google Scholar 

  76. Peek RM, Wirth HP, Moss SF, Yang M, Abdalla AM, Tham KT, et al.Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in Mongolian gerbils. Gastroenterology 2000;118:48–59.

    Article  PubMed  CAS  Google Scholar 

  77. Suzuki H, Nagahashi S, Seto K, Kai A, Suematsu M, Suzuki M, et al. Attenuated apoptosis inH. pylori-colonized gastric mucosa of Mongolian gerbils. Gastroenterology 2000;118:A746 (abstract).

    Google Scholar 

  78. Takashima M, Furuta T, Hanai H, Sugimura H, Kaneko E. The effects ofHelicobacter pylori on gastric acid secretion and serum gastrin levels in Mongolian gerbils with reference to interleukin-1B. Gastroenterology 2000;118:A746 (abstract).

    Google Scholar 

  79. Li H, Andersson EM, Heiander HF. Reactions from rat gastric mucosa during one year ofHelicobacter pylori infection. Dig Dis Sci 1999;44:116–24.

    Article  PubMed  CAS  Google Scholar 

  80. Wagner S, Beil W, Westermann J, Logan RP, Bock CT, Trautwein C, et al. Regulation of gastric epithelial cell growth byHelicobacter pylori: evidence for a major role of apoptosis. Gastroenterology 1997;113:1836–47.

    Article  PubMed  CAS  Google Scholar 

  81. Rudi J, Kuck D, Strand S, von Herbay A, Mariani SM, Krammer PH, et al. Involvement of the CD95 (APO-1/Fas) receptor and ligand system inHelicobacter pylori-induced gastric epithelial apoptosis. J Clin Invest 1998;102:1506–14.

    Article  PubMed  CAS  Google Scholar 

  82. Jones NL, Day AS, Jennings HA, Sherman PM.Helicobacter pylori induces gastric epithelial cell apoptosis in association with increased Fas receptor expression. Infect Immun 1999;67:4237–42.

    PubMed  CAS  Google Scholar 

  83. Houghton J, Macera-Bloch LS, Harrison L, Kim KH, Korah RM. Tumor necrosis factor alpha and interleukin 1beta upregulate gastric mucosal Fas antigen expression inHelicobacter pylori infection. Infect Immun 2000;68:1189–95.

    Article  PubMed  CAS  Google Scholar 

  84. Fan X, Crowe SE, Behar S, Gunasena H, Ye G, Haeberle H, et al. The effect of class II major histocompatibility complex expression on adherence ofHelicobacter pylori and induction of apoptosis in gastric epithelial cells: a mechanism for T helper cell type 1-mediated damage. J Exp Med 1998;187:1659–69.

    Article  PubMed  CAS  Google Scholar 

  85. Williams CS, Smalley W, DuBois RN. Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Invest 1997;100:1325–9.

    Article  PubMed  CAS  Google Scholar 

  86. Boolbol SK, Dannenberg AJ, Chadburn A, Martucci C, Guo XJ, Ramonetti JT, et al. Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 1996;56:2556–60.

    PubMed  CAS  Google Scholar 

  87. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994;107:1183–8.

    PubMed  CAS  Google Scholar 

  88. Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, et al. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996;87:803–9.

    Article  PubMed  CAS  Google Scholar 

  89. Ristimaki A, Honkanen N, Jankala H, Sipponen P, Harkonen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 1997;57:1276–80.

    PubMed  CAS  Google Scholar 

  90. Uefuji K, Ichikura T, Mochizuki H, Shinomiya N. Expression of cyclooxygenase-2 protein in gastric adenocarcinoma. J Surg Oncol 1998;69:168–72.

    Article  PubMed  CAS  Google Scholar 

  91. Farrow DC, Vaughan TL, Hansten PD, Stanford JL, Risch HA, Gammon MD, et al. Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 1998;7:97–102.

    PubMed  CAS  Google Scholar 

  92. Zaridze D, Borisova E, Maximovitch D, Chkhikvadze V. Aspirin protects against gastric cancer: results of a case-control study from Moscow, Russia. Int J Cancer 1999;82:473–6.

    Article  PubMed  CAS  Google Scholar 

  93. Sawaoka H, Kawano S, Tsuji S, Tsuji M, Sun W, Gunawan ES, et al.Helicobacter pylori infection induces cyclooxygenase-2 expression in human gastric mucosa. Prostaglandins Leukot Essent Fatty Acids 1998;59:313–16.

    Article  PubMed  CAS  Google Scholar 

  94. Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP, et al. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 inHelicobacter pylori gastritis. Gastroenterology 1999;116:1319–29.

    Article  PubMed  CAS  Google Scholar 

  95. McCarthy CJ, Crofford LJ, Greenson J, Scheiman JM. Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication ofHelicobacter pylori infection. Am J Gastroenterol 1999;94:1218–23.

    Article  PubMed  CAS  Google Scholar 

  96. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995;83:493–501.

    Article  PubMed  CAS  Google Scholar 

  97. Romano M, Ricci V, Memoli A, Tuccillo C, Di Popolo A, Sommi P, et al.Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandin E2 synthesis in MKN 28 gastric mucosal cells in vitro. J Biol Chem 1998;273:28560–3.

    Article  PubMed  CAS  Google Scholar 

  98. Wilson KT, Akhtar M, Magno RM, Ashktorab H, Smoot DT, Zhao HM. High output production of PGE2by COX-2 and inhibition of apoptosis inH. pylori-stimulated non-malignant gastric epithelial cells. Gastroenterology 2000;118:A182 (abstract).

    Article  Google Scholar 

  99. Nagayo T. Histogenesis and precursors of human gastric cancer. Berlin: Springer-Verlag, 1986.

    Google Scholar 

  100. Howson CP, Hiyama T, Wynder EL. The decline in gastric cancer: epidemiology of an unplanned triumph. Epidemiol Rev 1986;8:1–27.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Vanderbilt University School of Medicine, C-2104 Medical Center North, 37232-2279, Nashville, TN, USA

    Richard M. Peek

  2. Department of Veterans Affairs Medical Center, Nashville, TN, USA

    Richard M. Peek

Authors
  1. Richard M. Peek
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peek, R.M. Helicobacter pylori strain-specific modulation of gastric mucosal cellular turnover: implications for carcinogenesis. J Gastroenterol 37 (Suppl 13), 10–16 (2002). https://doi.org/10.1007/BF02990093

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02990093

Key words

Search

Navigation