Downregulated Expression of E-cadherin and TP53 in Patients with Gastric Diseases: the Involvement of H. pylori Infection and Its Virulence Markers
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Gastritis caused by infection with Helicobacter pylori is characterized by chronic inflammation and damage in gastric tissue, which is a main risk factor for gastric cancer. Associated with H. pylori, the TP53 gene tumor suppressor and the cell adhesion glycoprotein epithelial cadherin develop a relevant role in the integrity and carcinogenesis of the epithelium. We aimed to detection of H. pylori and its main virulence markers and measured the messenger RNA (mRNA) expression levels of E-cadherin and TP53 genes.
The detection of H. pylori and its virulence markers, as well as the mRNA expression levels of E-cadherin and TP53 genes, were obtained for 161 samples of gastric biopsies including 37 with normal gastric tissue, 70 with gastritis, 24 from neoplastic tissue, and 27 from adjacent non-neoplastic by means of a quantitative real-time polymerase chain reaction.
The mRNA expression levels of E-cadherin and TP53 were found to be decreased in patients with gastritis, independently of H. pylori infection. In samples from gastric patients, the neoplastic tissue showed an accentuated decrease of expression; on the other hand, the expression of E-cadherin was normal in adjacent non-neoplastic.
No evidence was found of the involvement of the cagA and vacA genes in the decreased expression of E-cadherin and TP53. The process of carcinogenesis is complex, and the decrease of the E-cadherin gene expression and TP53 gene expression appears to contribute significantly.
KeywordsE-cadherin Gastric cancer Gene expression Helicobacter pylori TP53
Compliance with Ethical Standards
Conflict of Interests
The authors declare that there is no conflict of interests.
The authors would like to thank the São Paulo Research Foundation (FAPESP) for the funding of this research (grant numbers 20012/18333-3, 2013/21224-4, and 2013/21285-3).
- 2.Schildberg CW, Abba M, Merkel S, Agaimy A, Dimmler A, Schlabrakowski A, et al. Gastric cancer patients less than 50 years of age exhibit significant downregulation of E-cadherin and CDX2 compared to older reference populations. Adv Med Sci. 2014;59(1):142–6. doi: 10.1016/j.advms.2014.03.002.CrossRefPubMedGoogle Scholar
- 5.Lazar D, Taban S, Sporea I, Dema A, Cornianu M, Lazar E, et al. The immunohistochemical expression of the p53-protein in gastric carcinomas. Correlation with clinicopathological factors and survival of patients. Romanian J Morphol Embryol Rev Roum Morphol Embryol. 2010;51(2):249–57.Google Scholar
- 7.Santos JC, Ladeira MS, Pedrazzoli Jr J, Ribeiro ML. Relationship of IL-1 and TNF-alpha polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population. Braz J Med Biol Res / Rev Bras Pesqui Med Biol / Soc Bras Biofisica. 2012;45(9):811–7.Google Scholar
- 12.Weydig C, Starzinski-Powitz A, Carra G, Lower J, Wessler S. CagA-independent disruption of adherence junction complexes involves E-cadherin shedding and implies multiple steps in Helicobacter pylori pathogenicity. Exp Cell Res. 2007;313(16):3459–71. doi: 10.1016/j.yexcr.2007.07.015.CrossRefPubMedGoogle Scholar
- 13.Watanabe T, Asano N, Fichtner-Feigl S, Gorelick PL, Tsuji Y, Matsumoto Y, et al. NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway. J Clin Invest. 2010;120(5):1645–62. doi: 10.1172/JCI39481.PubMedCentralCrossRefPubMedGoogle Scholar
- 14.Stolte M, Meining A. The updated Sydney system: classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol J Can Gastroenterol. 2001;15(9):591–8.Google Scholar
- 16.Pereira WN, Ferraz MA, Zabaglia LM, de Labio RW, Orcini WO, Ximenez JPB, Neto AC, Payão SLM, Rasmussen L (2014) Association among H. pylori virulence markers dupA, cagA and vacA in Brazilian patients. J Venomous Anim Toxins Incl Trop Dis 20 (1):5Google Scholar
- 18.Gomes LI, Rocha GA, Rocha AM, Soares TF, Oliveira CA, Bittencourt PF, et al. Lack of association between Helicobacter pylori infection with dupA-positive strains and gastroduodenal diseases in Brazilian patients. Int J Med Microbiol : IJMM. 2008;298(3–4):223–30. doi: 10.1016/j.ijmm.2007.05.006.CrossRefPubMedGoogle Scholar
- 20.Rasmussen LT, de Labio RW, Neto AC, Silva LC, Queiroz VF, Smith MAC, et al. Detection of Helicobacter pylori in gastric biopsies, saliva and dental plaques of dyspeptic patients from Marília, São Paulo, Brazil: presence of vacA and cagA genes. J Venomous Anim Toxins Incl Trop Dis. 2012;18(2):7. doi: 10.1590/S1678-91992012000200008.Google Scholar
- 23.Wroblewski LE, Shen L, Ogden S, Romero-Gallo J, Lapierre LA, Israel DA, et al. Helicobacter pylori dysregulation of gastric epithelial tight junctions by urease-mediated myosin II activation. Gastroenterology. 2009;136(1):236–46. doi: 10.1053/j.gastro.2008.10.011.PubMedCentralCrossRefPubMedGoogle Scholar
- 24.Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, et al. Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 2007;26(32):4617–26. doi: 10.1038/sj.onc.1210251.CrossRefPubMedGoogle Scholar
- 28.Liu Y, Chen XG, Liang CZ. Expressions of E-cadherin and N-cadherin in prostate cancer and their implications. Zhonghua Nan Ke Xue Natl J Androl. 2014;20(9):781–6.Google Scholar
- 29.Mehendiratta M, Solomon MC, Boaz K, Guddattu V, Mohindra A. Clinico-pathological correlation of E-cadherin expression at the invasive tumor front of Indian oral squamous cell carcinomas: an immunohistochemical study. J Oral Maxillofac Pathol : JOMFP. 2014;18(2):217–22. doi: 10.4103/0973-029X.140753.PubMedCentralCrossRefPubMedGoogle Scholar
- 32.Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, et al. ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Proc Natl Acad Sci U S A. 2005;102(26):9182–7. doi: 10.1073/pnas.0500918102.PubMedCentralCrossRefPubMedGoogle Scholar
- 36.Karim S, Ali A. Correlation of p53 over-expression and alteration in p53 gene detected by polymerase chain reaction-single strand conformation polymorphism in adenocarcinoma of gastric cancer patients from India. World J Gastroenterol : WJG. 2009;15(11):1381–7.PubMedCentralCrossRefPubMedGoogle Scholar
- 37.Ierardi E, Di Leo A, Barone M, Marangi S, Burattini O, Panarese A, et al. Tumor necrosis factor alpha and apoptosis in Helicobacter pylori related progressive gastric damage: a possible mechanism of immune system involvement in epithelial turnover regulation. Immunopharmacol Immunotoxicol. 2003;25(2):203–11.CrossRefPubMedGoogle Scholar