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8 - Helicobacter pylori mechanisms for inducing epithelial cell proliferation

Published online by Cambridge University Press:  15 September 2009

By
Michael Naumann  and
Jean E Crabtree
Edited by
Alistair J. Lax
Michael Naumann
Affiliation:
Institute of Experimental Internal Medicine, Medical Faculty, Otto-van-Guericke-University
Jean E Crabtree
Affiliation:
Molecular Medicine Unit, St James's University Hospital
Alistair J. Lax
Affiliation:
King's College London
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Summary

Helicobacter pylori, the first bacterium to be designated a Class I carcinogen, has a major aetiological role in human gastric carcinogenesis. H. pylori infection is acquired primarily in childhood and, in the majority of instances, infection and associated chronic gastritis are lifelong. A key feature of H. pylori infection of relevance to the associated increased risk of developing gastric cancer is the hyperproliferation of gastric epithelial cells induced by the bacterium. Infection is associated with increased gastric epithelial cell proliferation in both humans and in experimental animal models.

Clinically, there is a marked diversity in the outcome of H. pylori infection and only a few infected subjects will develop gastric cancer (reviewed Peek and Blaser, 2002). Recent studies in Japan show that the risk of cancer with H. pylori infection is greatest in infected subjects with nonulcer dyspesia or gastric ulceration who develop severe gastric atrophy and intestinal metaplasia (Uemura et al., 2001). Bacterial virulence factors such as the cag pathogenicity island (PAI) (Blaser et al., 1995; Kuipers et al., 1995; Webb et al., 1999) and genetic polymorphisms in the interleukin-1β and IL-1 receptor antagonist genes associated with overexpression of IL-1 and hypochlorhydria (El-Omar et al., 2000; Machado et al., 2001; Furuta et al., 2002) have each been linked to an increased risk of developing gastric atrophy and/or intestinal type gastric cancer.

H. pylori is one of several chronic infections that have recently been associated with the development of neoplasia (see Chapter 9).

Type
Chapter
Information
Bacterial Protein Toxins
Role in the Interference with Cell Growth Regulation
 , pp. 169 - 198
Publisher: Cambridge University Press
Print publication year: 2005

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References

Akanuma, M, Maeda, S, Ogura, K, Mitsuno, Y, Hirata, Y, Ikenoue, T, Otsuka, M, WatanabeT, T,Yamaji, Y, Yoshida, H, Kawabe, T, Shiratori, Y, and Omata, M (2002). The evaluation of putative virulence factor of Helicobacter pylori for gastroduodenal disease by use of a short term Mongolian gerbil infection model. J. Infect. Dis., 185, 341–347CrossRefGoogle Scholar
Akopyants, N S, Clifton, S W, Kersulyte, D, Crabtree, J E, Youree, B E, Reece, C A, Bukanov, N O, Drazek, S E, Roe, B A, and Berg, D E (1998). Analyses of the cag pathogenicity island of Helicobacter pylori. Mol. Microbiol., 28, 37–54CrossRefGoogle ScholarPubMed
Asahi, M, Azuma, T, Ito, S, Ito, Y, Suto, H, Nagai, Y, Tsubokawa, M, Tohyama, Y, Maeda, S, Omata, M, Suzuki, T, and Sasakawa, C (2000). Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J. Exp. Med., 191, 593–602CrossRefGoogle ScholarPubMed
Backert, S, Ziska, E, Brinkmann, V, Zimny-Arndt, U, Fauconnier, A, Jungblut, P R, Naumann, M, and Meyer, T F (2000). Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell. Microbiol., 2, 155–164CrossRefGoogle ScholarPubMed
Bardelli, A, Longati, P, Gramaglia, D, Basilico, C, Tamagnone, L, Giordano, S, Ballinari, D, Michieli, P, and Comoglio, P M (1998). Uncoupling signal transducers from oncogenic MET mutants abrogates cell transformation and inhibits invasive growth. Proc. Natl. Acad. Sci. USA, 95, 14379–14383CrossRefGoogle ScholarPubMed
Barnard, J A, Beauchamp, R D, Russell, W E, Dubois, R N, and Coffey, R J (1995). Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology. Gastroenterology, 108, 564–580CrossRefGoogle ScholarPubMed
Berg, D J, Lynch, N A, Lynch, R G, and Lauricella, D M (1998). Rapid development of severe hyperplastic gastritis with gastric epithelial dedifferentiation in Helicobacter felis-infected IL-10–/– mice. Am. J. Pathol., 152, 1377–1386Google Scholar
Blaser, M J, Perez-Perez, G I, Kleanthous, H, Cover, T L, Peek, R M, Chyou, P H, Stemmermann, G N, and Nomura, A (1995). Infection with Helicobacter pylori strains possessing cagA is associated with increased risk of developing adenocarcinoma of the stomach. Cancer Res., 55, 2111–2115Google ScholarPubMed
Brenes, F, Ruiz, B, Correa, P, Hunter, F, Rhamakrishnan, T, Fontham, E, and Shi, T Y (1993). Helicobacter pylori causes hyperproliferation of the gastric epithelium: Pre- and post-eradication indices of proliferating cell nuclear antigen. Am. J. Gastroenterol., 88, 1870–1875Google ScholarPubMed
Cahill, R J, Xia, H, Kilgallen, C, Beattie, S, Hamilton, H, and O'Morain, C (1995). Effect of eradication of Helicobacter pylori infection on gastric epithelial cell proliferation. Digest. Dis. Sci., 40, 1627–1631CrossRefGoogle ScholarPubMed
Cahill, R J, Kilgallen, C, Beatti, S, Hamilton, H, and O'Morain, C (1996). Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma. Gut, 38, 177–181CrossRefGoogle ScholarPubMed
Censini, S, Lange, C, Xiang, Z, Crabtree, J E, Ghiara, P, Borodovsky, M, Rappuoli, R, and Covacci, A (1996). cag, a pathogenicity island of Helicobacter pylori, encodes Type I-specific and disease-associated virulence factors. Proc. Natl. Acad. Sci. USA, 93, 14648–14653CrossRefGoogle ScholarPubMed
Churin, Y, Kardalinou, E, Meyer, T F, and Naumann, M (2001). Pathogenicity island-dependent activation of Rho GTPases Rac1 and Cdc42 in Helicobacter pylori infection. Mol. Microbiol., 40, 815–823CrossRefGoogle ScholarPubMed
Churin, Y, Al-Ghoul, L, Kepp, O, Meyer, T F, Birchmeier, W, and Naumann, M (2003). Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J. Cell Biol., 161, 249–255CrossRefGoogle ScholarPubMed
Comoglio, P M and Boccaccio, C (2001). Scatter factors and invasive growth. Semin. Cancer Biol., 11, 153–165CrossRefGoogle ScholarPubMed
Cook, P W, Pittelkow, M R, Keeble, W W, Graves-Deal, R, Coffey, R J, and Shipley, G D (1992). Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas. Cancer Res., 52, 3224–3227Google ScholarPubMed
Cox, J M, Clayton, C L, Tomita, T, Wallace, D M, Robinson, P A, and Crabtree, J E (2001). cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes. Infect. Immun., 69, 6970–6980CrossRefGoogle ScholarPubMed
Court, M, Robinson, P A, Dixon, M F, and Crabtree, J E (2002). Gastric Helicobacter species infection in murine and gerbil models: Comparative analysis of effects of H. pylori and H. felis on gastric epithelial cell proliferation. J. Infect. Dis., 186, 1348–1352CrossRefGoogle ScholarPubMed
Court, M, Robinson, P A, Dixon, M F, Jeremy, A H T, and Crabtree, J E (2003). The effect of gender on Helicobacter felis mediated gastritis, epithelial cell proliferation and apoptosis in the mouse model. J. Pathol., 201, 303–311CrossRefGoogle ScholarPubMed
Crabtree, J E, Taylor, J E, Wyatt, J I, Heatley, R V, Shallcross, T M, Tompkins, D S, and Rathbone, B J (1991). Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration and gastric pathology. Lancet 338, 332–335CrossRefGoogle ScholarPubMed
Crabtree, J E, Farmery, S M, Lindley, I J D, Figura, N, Peichl, P, and Tompkins, D S (1994a). CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cells. J. Clin. Pathol., 47, 945–950CrossRefGoogle Scholar
Crabtree, J E, Wyatt, J I, Trejdosiewicz, L K, Peichl, P, Nichols, P N, Ramsey, N, Primrose, J N, and Lindley, I J D (1994b). Interleukin-8 expression in Helicobacter pylori, normal and neoplastic gastroduodenal mucosa. J. Clin. Pathol., 47, 945–950CrossRefGoogle Scholar
Crabtree, J E, Ferrero, R L, and Kusters, J G (2002). The mouse colonizing Helicobacter pylori strain SS1 may lack a functional cag pathogenicity island. Helicobacter, 7, 139–140CrossRefGoogle Scholar
Ebert, M P, Yu, J, Sung, J J, and Malfertheiner, P (2000). Molecular alterations in gastric cancer: The role of Helicobacter pylori. Eur. J. Gastroenl. Hepat., 12, 795–798CrossRefGoogle ScholarPubMed
Eberhart, C E and Dubois, R N (1995). Eicosanoids and the gastrointestinal tract. Gastroenterology, 109, 285–301CrossRefGoogle ScholarPubMed
Eck, M, Schmausser, K, Scheller, A, Toksoy, A, Kraus, M, Menzel, T, Muller-Hermelink, H K, and Gillitzer, R (2000). CXC chemokines Groα/IL-8 and IP-10/MIG in Helicobacter pylori gastritis. Clin. Exp. Immunol., 122, 192–199CrossRefGoogle Scholar
El-Omar, E, Oien, K, El-Nujumi, A, Gillen, D, Wirz, A, Dahill, P, Williams, C, Ardhill, J E, and McColl, K E (1997). H. pylori infection and chronic gastric acid hyposecretion. Gastroenterology, 113, 15–24CrossRefGoogle ScholarPubMed
El-Omar, E M, Carrington, M, Chow, W H, McColl, K E, Bream, J H, Young, H A, Herrera, J, Lissowska, J, Yuan, C C, Rothman, N, Lanyon, G, Martin, M, Fraumeni, J F, and Rabkin, C S (2000). Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature, 404, 398–402CrossRefGoogle ScholarPubMed
El-Zimaity, H M, Graham, D Y, Genta, R M, and Lechago, J (2000). Sustained increase in gastric antral epithelial cell proliferation despite cure of Helicobacter pylori infection. Am. J. Gastroenterol., 95, 930–935CrossRefGoogle ScholarPubMed
Ferrero, R L, Ave, P, Radcliff, F J, Labigne, A, and Huerre, M R (2000). Outbred mice with long-term Helicobacter felis infection develop both gastric lymphoid tissue and glandular hyperplastic lesions. J. Pathol., 191, 333–3403.0.CO;2-H>CrossRefGoogle ScholarPubMed
Foryst-Ludwig, A and Naumann, M (2000). p21-activated kinase 1 activates the nuclear factor kappa B (NF-kappa B)-inducing kinase Iκ B kinases NFκ B pathway and proinflammatory cytokines in Helicobacter pylori infection. J. Biol. Chem., 275, 39779–39785CrossRefGoogle Scholar
Fox, J G, Li, X, Cahill, R J, Andrutis, K, Rustgi, A K, Odze, R, and Wang, T C (1996). Hypertrophic gastropathy in Helicobacter felis-infected wild-type C57BL/6 mice and p53 hemizygous transgenic mice. Gastroenterology, 110, 155–166CrossRefGoogle ScholarPubMed
Fox, J G, Dangler, C A, Whary, M T, Edelman, W, Kucherlapati, R, and Wang, T C (1997). Mice carrying a truncated Apc gene have diminished gastric epithelial proliferation, gastric inflammation and humoral immunity in response to Helicobacter felis infection. Cancer Res., 57, 3972–3978Google ScholarPubMed
Fox, J G, Dangler, C A, Taylor, N S, King, A, Koh, T J, and Wang, T C (1999). High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. Cancer Res., 59, 4823–4828Google ScholarPubMed
Fox, J G, Sheppard, B J, Dangler, C A, Whary, M T, Ihrig, M, and Wang, T C (2002). Germ-line p53-targeted disruption inhibits Helicobacter-induced premalignant lesions and invasive gastric carcinoma through down-regulation of Th1 proinflammatory responses. Cancer Res., 62, 696–702Google ScholarPubMed
Fraser, A G, Sim, R, Sankey, E A, Dhillon, A P, and Pounder, R E (1994). Effect of eradication of Helicobacter pylori on gastric epithelial cell proliferation. Aliment. Pharm. Therap., 8, 167–173CrossRefGoogle ScholarPubMed
Fu, S, Ramanujam, K S, Wong, A, Fantry, G T, Drachenberg, C B, James, S P, Meltzer, S J, and Wilson, K T (1999). Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology, 116, 1319–1329CrossRefGoogle ScholarPubMed
Furge, K A, Zhang, Y W, and Woude, G F (2000). Met receptor tyrosine kinase: Enhanced signaling through adapter proteins. Oncogene, 19, 5582–5589CrossRefGoogle ScholarPubMed
Furuta, T, El-Omar, E M, Xiao, F, Shirai, N, Takashima, M, and Sugimurra, H (2002). Interleukin 1ϐ polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan. Gastroenterology, 123, 92–105CrossRefGoogle ScholarPubMed
Fujiyama, K, Fujioka, T, Murakamik, K, and Naru, M (1995). Effects of Helicobacter pylori infection on gastric mucosal defence factors in Japanese monkeys. J. Gastroenterol., 30, 441–416CrossRefGoogle Scholar
Gooz, M, Gooz, P, and Smolka, A J (2001). Epithelial and bacterial metalloproteinases and their inhibitors in H. pylori infection of human gastric epithelial cells. Am. J. Physiol., 281, G823–G832Google Scholar
Gupta, R A, Polk, D B, Krishna, U, Israel, D A, Yan, F, DuBois, R N, and Peek, R M (2001). Activation of peroxisome proliferator-activated receptor γ suppresses nuclear factor κB–mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells. J. Biol. Chem., 276, 31059–31066CrossRefGoogle ScholarPubMed
Hahm, K B, Lee, K M M, Kim, Y B, Hong, W S, Lee, W H, Han, S U, Kim, M W, Ahn, B O, Oh, T Y, Lee, M H, Green, J, and Kim, S J (2002). Conditional loss of TGF-ϐ signalling leads to increased susceptibility to gastrointestinal carcinogenesis in mice. Aliment. Pharm. Therap., 16 (suppl. 2), 115–127CrossRefGoogle ScholarPubMed
Higashi, H, Tsutsumi, R, Muto, S, Sugiyama, T, Azuma, T, Asaka, M and Hatakeyama, M (2002a). SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science, 295, 683–686CrossRefGoogle Scholar
Higashi, H, Tsutsumi, R, Fujita, A, Yamazaki, S, Asaka, M, Azuma, T, and Hatakeyama, M (2002b). Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc. Natl. Acad. Sci. USA, 99, 14428–14433CrossRefGoogle Scholar
Hirata, Y, Maeda, S, Mitsuno, Y, Akanuma, M, Yamaji, Y, Ogura, K, Yoshida, H, Shiratori, Y, and Omata, M (2001). Helicobacter pylori activates the cyclin D1 gene through mitogen-activated protein kinase pathway in gastric cancer cells. Infect. Immun., 69, 3965–3971CrossRefGoogle ScholarPubMed
Houghton, J M, Bloch, L M, Goldstein, M, Hagen, S, and Korah, R M (2000). In vivo disruption of the Fas Pathway abrogates gastric growth alterations secondary to Helicobacter infection. J. Infect. Dis., 182, 856–864CrossRefGoogle ScholarPubMed
Ikeno, T, Ota, H, Sugiyama, A, Ishida, K, Katsuyama, T, Genta, R M, and Kwasaki, S (1999). Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils. Am. J. Pathol., 154, 951–960CrossRefGoogle ScholarPubMed
Ireton, K and Cossart, P (1998). Interaction of invasive bacteria with host signaling pathways. Curr. Opin. Cell Biol., 10, 276–283CrossRefGoogle ScholarPubMed
Israel, D A, Salama, N, Arnold, C N, Moss, S F, Ando, T, Wirth, H P, Tham, K T, Camorlinga, M, Blaser, M J, Falkow, S, and Peek, R M (2001). Helicobacter pylori strain specific differences in genetic content, identified by microarray, influence host inflammatory responses. J. Clin. Invest., 107, 611–620CrossRefGoogle ScholarPubMed
Izumi, Y, Hirata, M, Hasuwa, H, Iwamoto, R, Umata, T, Miyado, K, Tamai, Y, Kurisaki, T, Sehera-Fujisawa, A, Ohno, S, and Mekada, E (1998). A metalloprotease-disintegrin, MDC9/meltrin-γ/ADAM9 and PKCδ are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. EMBO J., 17, 7260–7272CrossRefGoogle ScholarPubMed
Jiang, H X, Pu, H, Huh, N H, Yokota, K, Oguma, K, and Namba, M (2001). Helicobacter pylori induces pepsinogen secretion by rat gastric cells in culture via a cAMP signal pathway. Int. J. Mol. Med., 7, 625–629Google Scholar
Jones, N L, Shannon, P T, Cutz, E, Yeger, H, and Sherman, P (1997). Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection. Am. J. Pathol., 151, 1695–1703Google ScholarPubMed
Jüttner, S, Cramer, T, Wessler, S, Walduck, A, Schmitz, F, Wunder, C, Weber, M, Fischer, S, Wiedenmann, B, Meyer, T F, Naumann, M, and Höcker, M (2003). Helicobacter pylori infection stimulates cyclooxygenase-2 gene expression in gastric epithelial cells: Essential role of pathogenicity island-independent activation of USF1/-2 and CREB transcription factors. Cell. Microbiol., 5, 821–834CrossRefGoogle Scholar
Kassis, J, Lauffenburger, D A, Turner, T, and Wells, A (2001). Tumor invasion as dysregulated cell motility. Semin. Cancer Biol., 11, 105–117CrossRefGoogle ScholarPubMed
Kawahara, T, Kuwano, Y, Teshima-Kondo, S, Sugiyama, T, Kawai, T, Nikawa, T, Kishi, K, and Rokutan, K (2001). Helicobacter pylori lipopolysaccharide from type I, but not type II strains, stimulates apoptosis of cultured gastric mucosal cells. J. Med. Invest., 48, 167–174Google Scholar
Keates, S, Keates, A C, Warny, M, Peek, R M, Murray, P G, and Kelly, C P (1999). Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag– Helicobacter pylori. J. Immunol., 163, 5552–5559Google ScholarPubMed
Keates, S, Sougioultzis, S, Keates, A, Zhao, D, Peek, R. M., Shaw, L M, and Kelly, C P (2001). cag+ Helicobacter pylori induce transactivation of the epidermal growth factor receptor in AGS gastric epithelial cells. J. Biol. Chem., 276, 48127–48134CrossRefGoogle ScholarPubMed
Kim, J S, Kim, J M, Jung, H C, and Song, I S (2001). Caspase-3 activity and expression of Bcl-2 family in human neutrophils by Helicobacter pylori water-soluble proteins. Helicobacter, 6, 207–215CrossRefGoogle ScholarPubMed
Klemke, R L, Cai, S, Giannini, A L, Gallagher, P J, Lanerolle, P, and Cheresh, D A (1997). Regulation of cell motility by mitogen-activated protein kinase. J. Cell Biol., 137, 481–492CrossRefGoogle ScholarPubMed
Kuipers, E J, Perez-Perez, G I, Meuwissen, S G M, and Blaser, M J (1995). H. pylori and atrophic gastritis: Importance of the cagA status. J. Natl. Cancer I., 87, 1777–1780CrossRefGoogle ScholarPubMed
Kurosawa, A, Miwa, H, Hirose, M, Tsune, I, Nagahara, A, and Sato, N (2002). Inhibition of cell proliferation and induction of apoptosis by Helicobacter pylori through increased phosphorylated p53, p21 and Bax expression in endothelial cells. J. Med. Microbiol., 51, 85–91CrossRefGoogle ScholarPubMed
Lee, A, O'Rourke, J, Corazon de Ungria, M, Robertson, B, DaskalopoulosG, G, and Dixon, M F (1997). A standardized mouse model of Helicobacter pylori infection: Introducing the Sydney strain. Gastroenterology, 112, 1386–1397CrossRefGoogle ScholarPubMed
Le'Negrate, G, Ricci, V, Hofman, V, Mograbi, B, Hofman, P, and Rossi, B (2001). Epithelial intestinal cell apoptosis induced by Helicobacter pylori depends on expression of the cag pathogenicity island phenotype. Infect. Immun., 69, 5001–5009CrossRefGoogle ScholarPubMed
Leung, W K, To, K F, Chan, F K L, Lee, T L, Chung, S C S, and Sung, J J Y (2000). Interaction of Helicobacter pylori eradication and non-steroidal anti-inflammatory drugs on gastric epithelial apoptosis and proliferation: Implications on ulcerogenesis. Aliment. Pharm. Therapeut., 14, 879–885CrossRefGoogle ScholarPubMed
Li, S D, Kersulyte, D, Lindley, I J D, Neelam, B, Berg, D E, and Crabtree, J E (1999). Multiple genes in the left half of the cag pathogenicity island of Helicobacter pylori are required for tyrosine kinase-dependent transcription of interleukin-8 in gastric epithelial cells. Infect. Immun., 67, 3893–3899Google ScholarPubMed
Liu, E S, Wong, B C, and Cho, C H (2001). Influence of gender difference and gastritis on gastric ulcer formation in rats. J. Gastroen. Hepatol., 16, 740–747CrossRefGoogle ScholarPubMed
Lynch, D A, Mapstone, N P, Clarke, A M, Jackson, P, Dixon, M F, Quirke, P, and Axon, A T (1995a). Cell proliferation in the gastric corpus in Helicobacter pylori associated gastritis and after gastric resection. Gut, 36, 351–353CrossRefGoogle Scholar
Lynch, D A, Mapstone, N P, Clarke, A M, Sobala, G M, Jackson, P, Morrison, L, Dixon, M F, Quirke, P, and Axon, A T (1995b). Cell proliferation in Helicobacter pylori associated gastritis and the effect of eradication therapy. Gut, 36, 346–350CrossRefGoogle Scholar
Lynch, D A F, Mapstone, N P, Clarke, A M T, Jackson, P, Moayyedi, P, Dixon, M F, Quirke, P, and Axon, A T R (1999). Correlation between epithelial cell proliferation and histological grading in gastric mucosa. J. Clin. Pathol., 52, 367–371CrossRefGoogle ScholarPubMed
Machado, J C, Pharoah, P, Sousa, S, Carvalho, R, Oliveira, C, Figueiredol, C, Amorim, A, Seruca, R, Caldas, C, Carneiro, F, and Sobrinho-Simoes, M (2001). Interleukin-1β and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology, 121, 823–829CrossRefGoogle Scholar
Maeda, S, Yoshida, H, Mitsuno, Y, Hirata, Y, Ogura, K, Shiratori, Y, and Omata, M (2002). Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori. Gut, 50, 771–778CrossRefGoogle ScholarPubMed
Matsumoto, K and Nakamura, T (1996). Heparin functions as a hepatotrophic factor by inducing production of hepatocyte growth factor. Biochem. Biophys. Res. Commun., 227, 455–461CrossRefGoogle ScholarPubMed
McCarthy, C J, Crofford, L J, Greenson, J, and Scheiman, J M (1999). Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication of Helicobacter pylori infection. Am. J. Gastroenterol., 94, 1218–1223CrossRefGoogle ScholarPubMed
Miehlke, S, Yu, J, Ebert, M, Szokodi, D, Vieth, M, Kuhlisch, E, Buchcik, R, Schimmin, W, Wehrmann, U, Malfertheiner, P, Ehninger, G, Bayerdorffer, E, and Stolte, M (2002). Expression of G1 phase cyclins in human gastric cancer and gastric mucosa of first-degree relatives. Digest. Dis. Sci., 47, 1248–1256CrossRefGoogle ScholarPubMed
Mitsuno, Y, Maeda, S, Yoshida, H, Hirata, Y, Ogura, K, Akanuma, M, Kawabe, T, Shiratori, Y, and Omata, M (2002). Helicobacter pylori activates the proto-oncogene c-fos through SRE transactivation. Biochem. Biophys. Res. Commun., 291, 868–874CrossRefGoogle ScholarPubMed
Miyazaki, Y, Shinomura, Y, Tsutsui, S, Zushi, S, Higashimoto, Y, Kanayama, S, Higashiyama, S, Taniguchi, N, and Matsuzawa, Y (1999). Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor. Gastroenterology, 116, 78–89CrossRefGoogle ScholarPubMed
Moss, S F, Sordillo, E M, Abdulla, A M, Makarov, V, Hanzely, Z, Perez-Perez, G I, Blaser, M J, and Holt, P R (2001). Increased gastric epithelial cell apoptosis associated with colonisation with cagA+ Helicobacter pylori strains. Cancer Res., 61, 1406–1411Google Scholar
Murayama, Y, Miyagawa, J, Shinomura, S, Kanayama, S, Isozaki, K, Mizuno, H, Ishiguro, S, Kiyohara, T, Miyazaki, Y, Taniguchi, N, Higahiyama, S, and Matsuzawa, Y (2002). Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer. Int. J. Cancer, 98, 505–513CrossRefGoogle ScholarPubMed
Naef, M, Yokoyama, M, Friess, H, Buchler, M W, and Korc, M (1996). Co-expression of heparin-binding EGF-like growth factor and related peptides in human gastric carcinoma. Int. J. Cancer, 66, 315–3213.0.CO;2-1>CrossRefGoogle ScholarPubMed
Naumann, M, Wessler, S, Bartsch, C, Wieland, B, Covacci, A, Haas, R, and Meyer, T F (1999). Activation of activator protein 1 and stress response kinases in epithelial cells colonized by Helicobacter pylori encoding the pathogenicity island. J. Biol. Chem., 274, 31655–31662CrossRefGoogle ScholarPubMed
Naumann, M (2001). Host cell signaling in Helicobacter pylori infection. Int. J. Med. Microbiol., 291, 299–305CrossRefGoogle ScholarPubMed
Naumann, Mand Crabtree, J E (2004). Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis. Trends Microbiol., 12, 29–36CrossRefGoogle ScholarPubMed
Nobes, C D and Hall, A (1999). Rho GTPases control polarity, protrusion, and adhesion during cell movement. J. Cell Biol., 144, 1235–1244CrossRefGoogle ScholarPubMed
Odenbreit, S, Puls, J, Sedlmaier, B, Gerland, E, Fischer, W, and Haas, R (2000). Translocation of CagA into epithelial cells by type IV secretion. Science, 287, 1497–1500CrossRefGoogle ScholarPubMed
Ogura, K, Maeda, S, Nakao, M, Watanabe, T, Tada, M, Kyutoku, T, Yoshida, H, Shiratori, Y, and Omata, M (2000). Virulence factors of Helicobacter pylori responsible for gastric diseases in Mongolian gerbil. J. Exp. Med., 192, 1601–1610CrossRefGoogle ScholarPubMed
Panella, C, Ierardi, E, Polimeno, L, Balzano, T, Ingrosso, M, Amoruso, A, Traversa, A, and Francavilla, A (1996). Proliferative activity of gastric epithelium in progressive stages of Helicobacter pylori infection. Digest. Dis. Sci., 41, 1132–1138CrossRefGoogle ScholarPubMed
Peek, R M, Moss, S F, Tham, K T, Perez-Perez, G I, Wang, S, Miller, G G, Atherton, J C, Holt, P R, and Blaser, M J (1997). Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation and apoptosis. J. Natl. Cancer I., 89, 863–868CrossRefGoogle Scholar
Peek, R M, Blaser, M J, Mays, D J, Forsyth, M H, Cover, T L, Song, S Y, Krishna, U, and Pietenpol, J A (1999). Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle. Cancer Res. 59, 6124–6131Google ScholarPubMed
Peek, R M, Wirth, H P, Moss, S F, Yang, M, Abdalla, A M, Tham, K T, Zhang, T, Tang, L H, Modlin, I M, and Blaser, M J (2000). Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in Mongolian gerbils. Gastroenterology, 118, 48–59CrossRefGoogle ScholarPubMed
Peek, R M and Blaser, M J (2002). Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat. Rev. Cancer, 2, 28–37CrossRefGoogle ScholarPubMed
Philpott, D J, Belaid, D, Troubadour, P, Thiberge, J M, Tankovic, J, Labigne, A, and Ferrero, R L (2002). Reduced activation of inflammatory responses in host cells by mouse-adapted Helicobacter pylori isolates. Cell. Microbiol., 4, 285–296CrossRefGoogle Scholar
Polat, A, Cinel, L, Dusmez, D, Aydin, O, and Egilmez, R (2002). Expression of cell-cycle related proteins in Helicobacter pylori gastritis and association with gastric carcinoma. Neoplasma, 49, 95–100Google ScholarPubMed
Pomorski, T, Meyer, T F, and Naumann, M (2001). Helicobacter pylori-induced prostaglandin E2 synthesis involves activation of cytosolic phospholipase A2 in epithelial cells. J. Biol. Chem., 276, 804–810CrossRefGoogle Scholar
Ponzetto, C, Bardelli, A, Zhen, Z, Maina, F, dalla Zonca, P, Giordano, S, Graziani, A, Panayotou, G, and Comoglio, P M (1994). A multifunctional docking site mediates signaling and transformation of the hepatocyte growth factor/scatter factor reception family. Cell, 77, 261–271CrossRefGoogle Scholar
Prenzel, N, Zwick, E, Daub, H, Leserer, M, Abraham, R, Wallasch, C, and Ullrich, A (1999). EGF receptor transactivation by G-protein-coupled receptors requires metalloprotease cleavage of proHB-EGF. Nature, 402, 884–88CrossRefGoogle ScholarPubMed
Rokkas, T, Ladas, S, Liatsos, C, Petridou, E, Papatheodorou, G, Theocharis, S, Karameris, A, and Raptis, S (1999). Relationship of Helicobacter pylori CagA status to gastric epithelial cell proliferation and apoptosis. Digest. Dis. Sci., 44, 487–493CrossRefGoogle ScholarPubMed
Romano, M, Ricci, V, Memoli, A, Tuccillo, C, Di Popolo, A, Sommi, P, Acquaviva, A M, Del Vecchio Blanco, C, Bruni, C B, and Zarrilli, R (1998). Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandidn E2 synthesis in MKN 28 gastric mucosal cells in vitro. J. Biol. Chem., 273, 28560–28563CrossRefGoogle Scholar
Romano, M, Ricci, V, Di Popolo Sommi, P, Del Vecchio Blanco, C, Bruni, C B, Ventura, U, Cover, T L, Blaser, M J, Coffey, R J, and Zarrilli, R (1998). Helicobacter pylori up-regulates expression of epidermal growth factor-related peptides, but inhibits their proliferative effect in MKN-28 gastric mucosal cells. J. Clin. Invest., 101, 1604–1613CrossRefGoogle Scholar
Roth, R A, Kapadia, S B, Martin, S M, and Lorenz, R G (1999). Cellular immune responses are essential for development of Helicobacter felis associated gastric pathology. J. Immunol., 163, 1490–1497Google ScholarPubMed
Rudi, J, Kuck, D, Strand, S, Herbay, A, Mariani, S M, Krammer, P H, Galle, P R, and Stremmel, W (1998). Involvement of the CD95 (APO1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis. J. Clin. Invest., 102, 1506–1514CrossRefGoogle Scholar
Sakagami, T, Dixon, M F, O'Rourke, J, Howlett, R, Alderuccio, F, Vella, J, Shimoyama, T, and Lee, A (1996). Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate from antral gastritis. Gut, 39, 639–648CrossRefGoogle ScholarPubMed
Satoh, K, Mutoh, H, Eda, A, Yanaka, I, Osawa, H, Honda, S, Kawata, H, Kihira, K, and Sugano, K (2002). Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: Effect of eradication of Helicobacter pylori. Helicobacter, 7, 192–198CrossRefGoogle ScholarPubMed
Sawaoka, H, Kawano, S, Tsuji, S, Tsuji, M, Sun, W, Gunawan, E S, and Hori, M (1998). Helicobacter pylori infection induces cyclooxygenase-2 expression in human gastric mucosa. Prostag. Leukotr. Ess., 59, 313–316CrossRefGoogle ScholarPubMed
Segal, E D, Cha, J, Falkow, S, and Tompkins, L S (1999). Altered states: Involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc. Natl. Acad. Sci. USA, 96, 14559–14564CrossRefGoogle ScholarPubMed
Sharma, S A, Tummuru, M K R, Miller, G G, and Blaser, M J (1995). Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect. Immun., 63, 1681–1687Google ScholarPubMed
Shen, Y, Naujokas, M, Park, M, and Ireton, K (2000). InlB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase. Cell, 103, 501–510CrossRefGoogle ScholarPubMed
Shirin, H, Sordillo, E M, Oh, S H, Yamamoto, H, Delohery, T, Weinstein, I B, and Moss, S F (1999). Helicobacter pylori inhibits the G1 to S transition in AGS gastric epithelial cells. Cancer Res., 59, 2277–2281Google Scholar
Shirin, H, Sordillo, E M, Kolevska, T K, Hibshoosh, H, Kawabata, Y, Oh, S H, Kuebler, J F, Delohery, T, Weghorst, C M, Weinstein, I B, and Moss, S F (2000). Chronic Helicobacter pylori infection induces an apoptosis-resistant phenotype associated with decreased expression of p27(kip1). Infect. Immun., 68, 5321–5328CrossRefGoogle Scholar
Smythies, L E, Waites, K B, Lindey, J R, Harris, P R, Ghiara, P, and Smith, P D (2000). Helicobacter pylori induced mucosal inflammation is Th1 mediated and exacerbated in IL-4 but not IFN γ gene deleted mice. J. Immunol., 165, 1022–1029CrossRefGoogle ScholarPubMed
Sommer, F, Faller, G, Rollinghoff, M, Kirchner, T, Mak, T W, and Lohoff, M (2001). Lack of gastritis and of an adaptive immune response in interferon regulatory factor-1 deficient mice infected with Helicobacter pylori. Eur. J. Immunol., 31, 396–4023.0.CO;2-Y>CrossRefGoogle ScholarPubMed
Sommi, P, Savio, M, Stivala, L A, Scotti, C, Mignosi, P, Prosperi, E, Vannini, V, and Solcia, E (2002). Helicobacter pylori releases factor(s) inhibiting cell cycle progression of human gastric cell lines by affecting cyclin E/cdk2 kinase activity and Rb protein phosphorylation through enhanced p27KIP1 protein expression. Exp. Cell Res., 281, 128–139CrossRefGoogle Scholar
Sozzi, M, Crosatti, M, Kim, S K, Romero, J, and Blaser, M J (2001). Heterogeneity of Helicobacter pylori cag genotypes in experimentally infected mice. FEMS Microbiol. Lett., 203, 109–114CrossRefGoogle ScholarPubMed
Stein, M, Rappuoli, R, and Covacci, A (2000). Tyrosine phosphorylation of Helicobacter pylori CagA antigen after cag driven host cell translocation. Proc. Natl. Acad. Sci. USA, 97, 1263–1268CrossRefGoogle ScholarPubMed
Suerbaum, S, Smith, J M, Bapumia, K, Morelli, G, Smith, N H, Kunstmann, E, Dyrek, I, and Achtman, M (1998). Free recombination within Helicobacter pylori. Proc. Natl. Acad. Sci. USA, 95, 12619–12624CrossRefGoogle ScholarPubMed
Sung, J J, Leung, W K, Go, M Y, To, K F, Cheng, A S, Ng, E K, and Chan, F K (2000). Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am. J. Pathol., 157, 729–35CrossRefGoogle ScholarPubMed
Suzuki, M, Raab, G, Moses, M A, Fernandez, C A, and Klagsbrun, M (1997). Matrix metalloprotease-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site. J. Biol. Chem., 272, 31730–31737CrossRefGoogle Scholar
Thiery, J P (2002). Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer, 2, 442–454CrossRefGoogle ScholarPubMed
Tsutsui, S, Shinomura, Y, Higashiyama, S, Higashimoto, Y, Miyasaki, Y, Kanayama, S, Hiraoka, S, Minami, T, Kitamura, S, Murayama, Y, Miyagawa, J, Taniguchi, N, and Matsuzawa, Y (1997). Induction of heparin binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach. Biochem. Biophys. Res. Commun., 235, 520–523CrossRefGoogle ScholarPubMed
Uemura, N, Okamoto, S, Yamamoto, S, Matsumura, N, Yamaguchi, S, Yamakido, M, Taniyama, K, Sasaki, N, and Schlemper, R J (2001). H. pylori infection and the development of gastric cancer. New Engl. J. Med., 345, 784–789CrossRefGoogle ScholarPubMed
Doorn, N E M, Namavar, F, Sparrius, M, Stoof, J, Rees, E P, Doorn, L J, and Vandenbrouke-Grauls, C M (1999). Helicobacter pylori-associated gastritis in mice is host and strain specific. Infect. Immun., 67, 3040–3046Google ScholarPubMed
Varro, A, Noble, P J, Wroblewski, L E, Bishop, L, and Dockray, G J (2002). Gastrin-cholecystokininB receptor expression in AGS cells is associated with direct inhibition and indirect stimulation of cell proliferation via paracrine activation of the epidermal growth factor receptor. Gut, 50, 827–833CrossRefGoogle Scholar
Wallasch, C, Crabtree, J E, Bevac, D, Robinson, P A, Wagner, H, and Ullrich, A (2002). Helicobacter pylori stimulated EGF receptor transactivation requires metalloprotease cleavage of HB-EGF. Biochem. Biophys. Res. Commun., 295, 695–701CrossRefGoogle ScholarPubMed
Wang, J, Fan, X, Lindholm, C, Bennett, M, O'Connoll, J, Shanahan, F, Brooks, E G, Reyes, V E, and Ernst, P B (2000a). Helicobacter pylori modulates lymphoepithelial cell interactions leading to epithelial cell damage through Fas/Fas Ligand interactions. Infect. Immun., 68, 4303–4311CrossRefGoogle Scholar
Wang, J, Court, M, Jeremy, A H T, Aboshkiwa, M A, Robinson, P A, and Crabtree, J E (2003). Infection of Mongolian gerbils with Chinese Helicobacter pylori strains. FEMS Immunol. Med. Mic., 36, 207–213CrossRefGoogle ScholarPubMed
Wang, T C, Koh, T J, Varro, A, Cahill, R J, Dangler, C A, Fox, J G, and Dockray, G J (1996). Processing and proliferative effects of human progastrin in transgenic mice. J. Clin. Invest., 98, 1918–1929CrossRefGoogle ScholarPubMed
Wang, T C, Goldenring, J R, Dangler, C, Ito, S, Mueller, A, Jeon, W K, Koh, T J, and Fox, J G (1998). Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection. Gastroenterology, 114, 675–89CrossRefGoogle ScholarPubMed
Wang, T C, Dangler, C A, Chen, D, Goldenring, J R, Koh, T, Raychowdhury, R, Coffey, R J, Ito, S, Varro, A, Dockray, G J, and Fox, J G (2000b). Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology, 118, 36–47CrossRefGoogle Scholar
Watanabe, T, Tada, M, Nagai, H, Sasaki, S, and Nakao, M (1998). Helicobacter pylori infection induces gastric cancer in Mongolian Gerbils. Gastroenterology, 115, 642–642CrossRefGoogle ScholarPubMed
Webb, P M, Crabtree, J E, and Forman, D (1999). Gastric cancer, cytotoxin-associated gene A positive H. pylori and serum pepsinogens: An international study. Gastroenterology, 116, 269–276CrossRefGoogle ScholarPubMed
Weel, J F L, Hulst, R W M, Gerrits, Y, Roorda, P, Feller, M, Dankert, J, Tytgat, G N J, and Ende, A (1996). The interrelationship between cytotoxin-associated gene A, vacuolating cytotoxin, and Helicobacter pylori-related diseases. J. Infect. Dis., 173, 1171–1175CrossRefGoogle ScholarPubMed
Weidner, K M, Di Cesare, S, Sachs, M, Brinkmann, V, Behrens, J, and Birchmeier, W (1996). Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature, 384, 173–176CrossRefGoogle ScholarPubMed
Wessler, S, Hocker, M, Fischer, W, Wang, T C, Rosewicz, S, Haas, R, Wiedenmann, B, Meyer, T F, and Naumann, M (2000). Helicobacter pylori activates the histidine decarboxylase promoter through a mitogen-activated protein kinase pathway independent of pathogenicity island-encoded virulence factors. J. Biol. Chem., 275, 3629–3636CrossRefGoogle ScholarPubMed
Wessler, S, Rapp, U R, Wiedenmann, B, Meyer, T F, Schoneberg, T, Hocker, M, and Naumann, M (2002). B-Raf/Rap1 signaling, but not c-Raf-1/Ras, induces the histidine decarboxylase promoter in Helicobacter pylori infection. FASEB J., 16, 417–419CrossRefGoogle Scholar
Wirth, H P, Beins, M H, Yang, M, Tham, K T, and Blaser, M J (1998). Experimental infection of Mongolian gerbils with wild-type and mutant Helicobacter pylori strains. Infect. Immun., 66, 4856–4866Google ScholarPubMed
Wong, B C, Wang, W P, So, W H, Shin, V Y, Wong, W M, Fung, F M, Liu, E S, Hiu, W M, Lam, S K, and Cho, C H (2001). Epidermal growth factor and its receptor in chronic active gastritis and gastroduodenal ulcer before and after Helicobacter pylori eradication. Aliment. Pharm. Therap., 15, 1459–1465CrossRefGoogle ScholarPubMed
Xia, H H and Talley, N J (2001). Apoptosis in gastric epithelium induced by Helicobacter pylori infection: Implications in gastric carcinogenesis. Am. J. Gastroenterol., 96, 16–26CrossRefGoogle ScholarPubMed
Xie, H, Pallero, M A, Gupta, K, Chang, P, Ware, M F, Witke, W, Kwiatkowski, D J, Lauffenburger, D A, Murphy-Ullrich, J E, and Wells, A (1998). EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCγ signaling pathway. J. Cell Sci., 111, 615–624Google ScholarPubMed
Yoshimura, T, Tomita, T, Dixon, M F, Axon, A T R, Robinson, P A, and Crabtree, J E (2002). ADAMs (A Disintegrin and Metalloproteinase) messenger RNA expression in H. pylori-infected, normal and neoplastic gastric mucosa. J. Infect. Dis., 185, 332–340CrossRefGoogle Scholar
Yu, J, Russell, R M, Saloman, R N, Murphy, J C, Palley, L S, and Fox, J G (1995). Effect of Helicobacter mustelae infection on ferret gastric epithelial cell proliferation. Carcinogenesis, 16, 1927–1931CrossRefGoogle ScholarPubMed
Yu, J, Leung, W K, Ng, E K, To, K F, Ebert, M P, Go, M Y, Chan, W Y, Chan, F K, Chung, S C, Malfertheiner, P, and Sung, J J (2001). Effect of Helicobacter pylori eradication on expression of cyclin D2 and p27 in gastric intestinal metaplasia. Aliment. Pharm. Therapeut., 15, 1505–1511CrossRefGoogle ScholarPubMed
Yu, J, Leung, W K, Go, M Y Y, Chan, M C W, To, K F, Ng, E K W, Chan, F K L, Ling, T K W, Chung, S C S, and Sung, J J Y (2002). Relationship between Helicobacter pylori babA2 status with gastric epithelial cell turnover and premalignant lesions. Gut, 51, 480–484CrossRefGoogle Scholar

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