Abstract

Helicobacter pylori (H. pylori) is a spiral-shaped Gram-negative bacterium that causes the most common chronic infection in the human stomach. Approximately 1%-3% of infected individuals develop gastric cancer. However, the mechanisms by which H. pylori induces gastric cancer are not completely understood. The available evidence indicates a strong link between the virulence factor of H. pylori, cytotoxin-associated gene A (CagA), and gastric cancer. To further characterize H. pylori virulence, we established three cell lines by infecting the gastric cancer cell lines SGC-7901 and AGS with cagA+ H. pylori and transfecting SGC-7901 with a vector carrying the full-length cagA gene. We detected 135 differently expressed proteins from the three cell lines using proteome technology, and 10 differential proteins common to the three cell lines were selected and identified by LC-MS/MS as well as verified by western blot: β-actin, L-lactate dehydrogenase (LDH), dihydrolipoamide dehydrogenase (DLD), pre-mRNA-processing factor 19 homolog (PRPF19), ATP synthase, calmodulin (CaM), p64 CLCP, Ran-specific GTPase-activating protein (RanGAP), P43 and calreticulin. Detection of the expression of these proteins and genes encoding these proteins in human gastric cancer tissues by real-time PCR (RT-qPCR) and western blot revealed that the expression of β-ACTIN, LDH, DLD, PRPF19 and CaM genes were up-regulated and RanGAP was down-regulated in gastric cancer tissues and/or metastatic lymph nodes compared to peri-cancerous tissues. High gene expression was observed for H. pylori infection in gastric cancer tissues. Furthermore, the LDH, DLD and CaM genes were demethylated at the promoter -2325, -1885 and -276 sites, respectively, and the RanGAP gene was highly methylated at the promoter -570 and -170 sites in H. pylori-infected and cagA-overexpressing cells. These results provide new insights into the molecular pathogenesis and treatment targets for gastric cancer with H. pylori infection.

Highlights

  • Helicobacter pylori (H. pylori) causes the most common chronic stomach infection in humans worldwide

  • Because cytotoxin-associated gene A (CagA) of H. pylori is a critical virulence factor in the development and progression of gastric cancer, CagA was detected in gastric cancer cell lines by RT-PCR and western blot after infection of SGC-7901 and AGS cells with H. pylori and transfection of SGC-7901 cells with cytotoxin-associated gene A gene (cagA)-vector

  • The CagA protein began to appear at a ratio of cells to bacteria of 1:500 in cultured cells at 6 h, and the content was highest at a ratio of 1:1000 at 6 h (Fig 1A and 1B)

Read more

Summary

Introduction

Helicobacter pylori (H. pylori) causes the most common chronic stomach infection in humans worldwide. Half of the world’s population is infected with H. pylori, and the majority of colonized individuals develop asymptomatic gastritis. Approximately 10%-20% of individuals develop peptic ulcer diseases and 1%-3% develop gastric cancer [1,2]. In 1994, H. pylori was classified as a type I carcinogen for gastric cancer by the World Health Organization’s International Agency for Research on Cancer. Gastric cancer is one of the most common types of cancers, and more than 70% of new cases and deaths occur in developing countries [3]. The global incidence rate has been declining for several decades, gastric cancer remains prevalent in most developing countries, including Japan, Korea and China [4,5,6]. In 2012, the Chinese Cancer Registry Annual Report indicated that gastric cancer morbidity and mortality are second and third among all malignant tumors, respectively

Objectives
Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.