title: Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis.
abstract: Chronic colonization of the human stomach by Helicobacter pylori, a Gram-negative bacterium, is the major cause of chronic gastritis, peptic ulcers and gastric cancer. Recent progress has elucidated important bacterial and host factors that are responsible for H. pylori-induced gastric inflammation and gastric malignancy. H. pylori cytotoxin-associated antigen A is the major oncogenic factor injected into host cells from bacteria and it disrupts epithelial cell functions. Together with H. pylori cag pathogenicity island, it causes general inflammatory stress within gastric mucosa and activates multiple oncogenic pathways in epithelial cells. A growing list of these pathways includes NF-kappaB, activator protein-1, PI3K, signal transducers and activators of transcription 3, Wnt/beta-catenin and cyclooxygenase 2. H. pylori induces epigenetic alterations, such as DNA methylation and histone modification, which play critical roles in oncogenic transformation. In addition, investigations into gastric stem cell or progenitor cell biology have shed light on the mechanisms through which gastric cancer may originate. Continued investigation in these areas will yield novel insights and help to elucidate the mechanisms of bacteria-induced carcinogenesis.
authors.affiliation: Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA. song.ding@uky.edu
authors.forename: Song-Ze
authors.initials: SZ
authors.lastname: Ding
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
authors.forename: Masanori
authors.initials: M
authors.lastname: Hatakeyama
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology*
references.citation: Cell Microbiol. 2009 Jan;11(1):70-82
references.pmid: 18782353
references.citation: Cancer Cell. 2008 Nov 4;14(5):408-19
references.pmid: 18977329
references.citation: Oncogene. 2007 Jul 12;26(32):4617-26
references.pmid: 17237808
references.citation: Biochem Biophys Res Commun. 2008 May 2;369(2):526-31
references.pmid: 18302936
references.citation: Lancet Oncol. 2008 Feb;9(2):139-48
references.pmid: 18207460
references.citation: Gastroenterology. 2007 Apr;132(4):1309-19
references.pmid: 17408661
references.citation: Ann N Y Acad Sci. 2003 Mar;983:220-31
references.pmid: 12724227
references.citation: Cancer. 2006 Mar 15;106(6):1250-9
references.pmid: 16475210
references.citation: J Immunol. 2006 Dec 1;177(11):7950-8
references.pmid: 17114467
references.citation: Eur J Cancer. 2001 Oct;37 Suppl 8:S4-66
references.pmid: 11602373
references.citation: Clin Cancer Res. 2003 Dec 15;9(17):6410-8
references.pmid: 14695142
references.citation: Cancer Res. 2003 Nov 1;63(21):7068-75
references.pmid: 14612497
references.citation: Gastroenterology. 2006 Oct;131(4):1086-95
references.pmid: 17030179
references.citation: Br J Cancer. 2007 Jul 2;97(1):1-5
references.pmid: 17592497
references.citation: Science. 2004 Nov 26;306(5701):1568-71
references.pmid: 15567866
references.citation: Cancer Res. 2003 Dec 15;63(24):8606-13
references.pmid: 14695171
references.citation: Mol Microbiol. 2001 May;40(4):815-23
references.pmid: 11401689
references.citation: PLoS One. 2010 Apr 01;5(4):e9875
references.pmid: 20368982
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10646-51
references.pmid: 16027366
references.citation: Virchows Arch. 2001 Oct;439(4):512-22
references.pmid: 11710638
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1003-8
references.pmid: 18192401
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5186-91
references.pmid: 15795379
references.citation: Epigenetics. 2009 Nov 16;4(8):577-86
references.pmid: 20081355
references.citation: Lab Invest. 2008 Mar;88(3):328-36
references.pmid: 18180700
references.citation: Mol Pharmacol. 2004 Dec;66(6):1465-77
references.pmid: 15456896
references.citation: Ann Surg Oncol. 2008 Jul;15(7):1968-76
references.pmid: 18470569
references.citation: Differentiation. 2001 Aug;68(1):13-21
references.pmid: 11683489
references.citation: Nat Med. 2007 Apr;13(4):470-6
references.pmid: 17401375
references.citation: Lab Invest. 2004 Apr;84(4):479-84
references.pmid: 14968123
references.citation: Gastroenterology. 2000 Jan;118(1):36-47
references.pmid: 10611152
references.citation: EMBO J. 2008 Jun 18;27(12):1671-81
references.pmid: 18511911
references.citation: EMBO J. 2003 Feb 3;22(3):515-28
references.pmid: 12554652
references.citation: Ann N Y Acad Sci. 2007 Apr;1100:60-74
references.pmid: 17460165
references.citation: Dig Dis. 2007;25(3):225-9
references.pmid: 17827945
references.citation: Int J Cancer. 2004 Jun 10;110(2):212-8
references.pmid: 15069684
references.citation: Curr Opin Gastroenterol. 2005 Nov;21(6):653-9
references.pmid: 16220040
references.citation: Cancer Sci. 2003 Aug;94(8):692-8
references.pmid: 12901794
references.citation: Science. 2003 May 30;300(5624):1430-4
references.pmid: 12775840
references.citation: Nature. 2007 May 17;447(7142):330-3
references.pmid: 17507984
references.citation: J Infect Dis. 2009 Mar 1;199(5):641-51
references.pmid: 19199544
references.citation: Nature. 1997 Aug 7;388(6642):539-47
references.pmid: 9252185
references.citation: Nature. 2007 Oct 18;449(7164):862-6
references.pmid: 17943123
references.citation: Carcinogenesis. 2006 Jun;27(6):1121-5
references.pmid: 16699174
references.citation: Tumour Biol. 2004 May-Jun;25(3):134-40
references.pmid: 15361710
references.citation: Ann N Y Acad Sci. 2008 Sep;1138:162-8
references.pmid: 18837897
references.citation: Cancer Invest. 2009 May;27(4):459-65
references.pmid: 19160099
references.citation: Cancer Res. 2009 Jan 15;69(2):632-9
references.pmid: 19147578
references.citation: J Gastroenterol Hepatol. 2009 Apr;24(4):646-51
references.pmid: 19175826
references.citation: J Exp Med. 2005 Nov 7;202(9):1235-47
references.pmid: 16275761
references.citation: Gut. 2006 Apr;55(4):463-8
references.pmid: 16428266
references.citation: Br J Cancer. 2002 Jun 5;86(11):1817-23
references.pmid: 12087472
references.citation: Science. 2002 Jan 25;295(5555):683-6
references.pmid: 11743164
references.citation: Genes Dev. 2001 Sep 15;15(18):2343-60
references.pmid: 11562345
references.citation: Oncogene. 2003 Oct 9;22(44):6946-53
references.pmid: 14534543
references.citation: Cancer Res. 2008 Jan 15;68(2):379-87
references.pmid: 18199531
references.citation: Int J Cancer. 2008 Feb 15;122(4):823-31
references.pmid: 17960618
references.citation: J Pathol. 2006 Jan;208(2):233-48
references.pmid: 16362989
references.citation: Gastroenterology. 2007 Mar;132(3):1009-23
references.pmid: 17383424
references.citation: Lab Invest. 2008 Feb;88(2):153-60
references.pmid: 18059362
references.citation: Hum Immunol. 2009 Nov;70(11):935-45
references.pmid: 19664671
references.citation: Oncogene. 2003 Jun 19;22(25):3943-51
references.pmid: 12813468
references.citation: Mol Cell. 2002 Oct;10(4):745-55
references.pmid: 12419219
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):989-95
references.pmid: 16467114
references.citation: Curr Opin Cell Biol. 2003 Apr;15(2):172-83
references.pmid: 12648673
references.citation: Nat Immunol. 2004 Nov;5(11):1166-74
references.pmid: 15489856
references.citation: Oncogene. 2005 Dec 1;24(54):8051-60
references.pmid: 16103878
references.citation: Nat Genet. 2008 Jun;40(6):741-50
references.pmid: 18488029
references.citation: Gastroenterology. 2004 Nov;127(5):1446-62
references.pmid: 15521014
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9661-6
references.pmid: 15980153
references.citation: Oncogene. 2008 Nov 24;27(55):7047-54
references.pmid: 19029944
references.citation: Mol Microbiol. 2002 Feb;43(4):971-80
references.pmid: 11929545
references.citation: Gastroenterology. 2006 Jan;130(1):188-206; quiz 212-3
references.pmid: 16401482
references.citation: Clin Cancer Res. 2005 Feb 1;11(3):1021-7
references.pmid: 15709167
references.citation: J Biol Chem. 2006 Nov 17;281(46):34888-96
references.pmid: 16990273
references.citation: J Gastroenterol. 2006 May;41(5):401-7
references.pmid: 16799880
references.citation: Cancer Res. 2004 Sep 15;64(18):6410-5
references.pmid: 15374948
references.citation: Appl Immunohistochem Mol Morphol. 2006 Sep;14(3):296-302
references.pmid: 16932020
references.citation: J Pathol. 2005 Jan;205(1):65-73
references.pmid: 15586362
references.citation: Gastroenterology. 2009 Oct;137(4):1367-79.e1-6
references.pmid: 19622359
references.citation: Proteomics. 2004 Oct;4(10):2961-8
references.pmid: 15378755
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14559-64
references.pmid: 10588744