Molecular biology of gastric cancer: Helicobacter infection and gastric adenocarcinoma: bacterial and host factors responsible for altered growth signaling

Stoicov, Calin; Saffari, Reza; Cai, Xueli; Hasyagar, Chhaya; Houghton, JeanMarie

doi:10.1016/j.gene.2004.07.023

Cited by 82 publications

(64 citation statements)

References 149 publications

(141 reference statements)

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“…Similarly, a high susceptibility to gastric adenocarcinoma has been observed in H. pylori-infected male INS-GAS mice (21,22,41). These findings are consistent with the high incidence of HCC and gastric adenocarcinoma in men (2,57).…”

Section: Discussionsupporting

confidence: 72%

Genetic Susceptibility to Chronic Hepatitis Is Inherited Codominantly in Helicobacter hepaticus -Infected AB6F1 and B6AF1 Hybrid Male Mice, and Progression to Hepatocellular Carcinoma Is Linked to Hepatic Expression of Lipogenic Genes and Immune Function-Associated Networks

et al. 2008

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Helicobacter hepaticus causes hepatitis in susceptible strains of mice. Previous studies indicated that A/JCr mice are susceptible and C57BL/6NCr mice are resistant to H. hepaticus-induced hepatitis. We used F1 hybrid mice derived from A/J and C57BL/6 matings to investigate their phenotype and determine their hepatic gene expression profile in response to H. hepaticus infection. F1 hybrid mice, as well as parental A/J and C57BL/6 mice, were divided equally into control and H. hepaticus-infected groups and euthanized at 18 months postinoculation. Hepatic lesions were evaluated histologically and the differential hepatic gene expression in F1 mice was determined by microarray-based global gene expression profiling analysis. H. hepaticus-infected parental strains including A/J and C57BL/6 mice, as well as F1 mice, developed significant hepatitis. Overall, hepatocellular carcinomas or dysplastic liver lesions were observed in 69% of H. hepaticus-infected F1 male mice and H. hepaticus was isolated from hepatic tissues of all F1 mice with liver tumors. Liver tumors, characterized by hepatic steatosis, developed in livers with high hepatitis scores. To identify gene expression specific to H. hepaticus-induced hepatitis and progression to hepatocellular carcinoma in F1 mice, a method using comparative group transcriptome analysis was utilized. The canonical pathway most significantly enriched was immunological disease. Fatty acid synthase and steaoryl-coenzyme A desaturase, the two rate-limiting enzymes in lipogenesis, were upregulated in neoplastic relative to dysplastic livers. This study suggests a synergistic interaction between hepatic steatosis and infectious hepatitis leading to hepatocellular carcinoma. The use of AB6F1 and B6AF1 mice, as well as genetically engineered mice, on a C57BL/6 background will allow studies investigating the role of chronic microbial hepatitis and steatohepatitis in the pathogenesis of liver cancer.

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Section: Discussionsupporting

confidence: 72%

Genetic Susceptibility to Chronic Hepatitis Is Inherited Codominantly in Helicobacter hepaticus -Infected AB6F1 and B6AF1 Hybrid Male Mice, and Progression to Hepatocellular Carcinoma Is Linked to Hepatic Expression of Lipogenic Genes and Immune Function-Associated Networks

et al. 2008

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“…C hronic infection by Helicobacter pylori, a Gram-negative bacterium, can lead to various gastrointestinal diseases, including chronic gastritis, gastric and duodenal ulceration, and gastric cancer (1)(2)(3)(4). After successful isolation and culture of H. pylori from patients with gastritis Ϸ20 years ago by Marshall and Warren (5), the complete genome sequences of various H. pylori strains have been identified (6).…”

mentioning

confidence: 99%

The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function

Chuang

Wu²,

Lo³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

132

105

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Helicobacter pylori, an oxygen-sensitive microaerophilic bacterium, contains many antioxidant proteins, among which alkylhydroperoxide reductase (AhpC) is the most abundant. The function of AhpC is to protect H. pylori from a hyperoxidative environment by reduction of toxic organic hydroperoxides. We have found that the sequence of AhpC from H. pylori is more homologous to mammalian peroxiredoxins than to eubacterial AhpC. We have also found that the protein structure of AhpC could shift from lowmolecular-weight oligomers with peroxide-reductase activity to high-molecular-weight complexes with molecular-chaperone function under oxidative stresses. Time-course study by following the quaternary structural change of AhpC in vivo revealed that this enzyme changes from low-molecular-weight oligomers under normal microaerobic conditions or short-term oxidative shock to high-molecular-weight complexes after severe long-term oxidative stress. This study revealed that AhpC of H. pylori acts as a peroxide reductase in reducing organic hydroperoxides and as a molecular chaperone for prevention of protein misfolding under oxidative stress.peroxiredoxin ͉ oxidative stress ͉ phylogenetic comparison ͉ dual functionality ͉ quaternary structural change

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“…On the other hand, H. pylori virulence factors also play a role in pathogenesis, since virulent strains are associated with more aggressive tissue damage and an increased risk of a severe clinical outcome (8). Finally, environmental factors such as nutrition are also thought to be important (38). Thus, the disease outcome is determined by a combination of host, bacterial, and environmental factors.…”

mentioning

confidence: 99%

Analysis of Cell Type-Specific Responses Mediated by the Type IV Secretion System of Helicobacter pylori

et al. 2005

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Helicobacter pylori persistently infects the human stomach and can cause gastritis, gastric ulceration, and gastric cancer. The type IV secretion system (TFSS) of virulent H. pylori strains translocates the CagA protein, inducing the dephosphorylation of host cell proteins and leading to changes in the morphology or shape of AGS gastric epithelial cells. Furthermore, the TFSS is involved in the induction of proinflammatory cytokines. While the H. pylori genes required for TFSS function have been investigated systematically, little is known about possible host cell factors involved. We infected 19 different mammalian cell lines individually with H. pylori and analyzed CagA translocation, dephosphorylation of host cell proteins, chemokine secretion (interleukin-8 and macrophage inflammatory protein 2), and changes in cellular phenotypes. Our results demonstrate that not only bacterial but also host cell factors determine the cellular response to infection. The identification of such unknown host cell factors will add to our understanding of host-pathogen interactions and might help in the development of new therapeutic strategies.

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Molecular biology of gastric cancer: Helicobacter infection and gastric adenocarcinoma: bacterial and host factors responsible for altered growth signaling

Cited by 82 publications

References 149 publications

Genetic Susceptibility to Chronic Hepatitis Is Inherited Codominantly in Helicobacter hepaticus -Infected AB6F1 and B6AF1 Hybrid Male Mice, and Progression to Hepatocellular Carcinoma Is Linked to Hepatic Expression of Lipogenic Genes and Immune Function-Associated Networks

Genetic Susceptibility to Chronic Hepatitis Is Inherited Codominantly in Helicobacter hepaticus -Infected AB6F1 and B6AF1 Hybrid Male Mice, and Progression to Hepatocellular Carcinoma Is Linked to Hepatic Expression of Lipogenic Genes and Immune Function-Associated Networks

The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function

Analysis of Cell Type-Specific Responses Mediated by the Type IV Secretion System of Helicobacter pylori

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