Article

Eradication of Helicobacter pylori reduced the immunohistochemical detection of p53 and MDM2 in gastric mucosa.

Department of General Medicine, Faculty of Medicine, Oita University, Hasama-machi, Oita 879-5593, Japan.
Journal of Gastroenterology and Hepatology (impact factor: 2.87). 07/2005; 20(6):941-6. DOI:10.1111/j.1440-1746.2005.03880.x pp.941-6
Source: PubMed

ABSTRACT Although Helicobacter pylori has been regarded as a pathogen of gastric cancer, the mechanism by which H. pylori is involved in gastric carcinogenesis remains unknown. To clarify the role of H. pylori in carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori eradication.
Biopsy specimens were obtained from 31 patients with H. pylori-infected gastric mucosa. Endoscopic biopsies were repeated 6 months after successful eradication. In addition, biopsy specimens from 12 patients with non-infected gastric mucosa were obtained. Immunohistochemical analysis was performed on the specimens using primary antibodies specific for p53 and MDM2.
Six months after H. pylori eradication, labeling indices for p53 were significantly reduced in the gastric corpus (2.3-fold; P < 0.01), and in the gastric antrum (2.0-fold; P < 0.01). Similarly, labeling indices for MDM2 were significantly reduced in the corpus (1.7-fold; P < 0.01), and in the antrum (3.5-fold; P < 0.01). In the non-infected group, labeling indices for p53 and MDM2 in the gastric mucosa were significantly lower (P < 0.01) than those of the H. pylori-infected group.
A significant increase is shown in p53 and MDM2 expression in H. pylori-infected gastric mucosa as compared to normal gastric mucosa; but successful eradication of H. pylori dramatically reduced the p53 and MDM2 levels. Therefore, H. pylori infection may be associated with alteration of cell proliferation and apoptosis.

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    Article: The Expression of Murine Double Minute 2 (MDM2) on Helicobacter pylori-Infected Intestinal Metaplasia and Gastric Cancer.
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    ABSTRACT: The overexpression of murine double minute 2 (MDM2) is found in several human tumors, and increased expression of MDM2 inactivates the apoptotic and cell cycle arrest function of p53. Interleukin-16 (IL-16) is a pleiotrophic cytokine and the properties of IL-16 suggest that it involve in the pathophysiological process of chronic inflammatory diseases. In this study, we investigated the expression of MDM2 in intestinal metaplasia and gastric cancer as well as the effect of H. pylori infection and IL-16 on epithelial cell proliferation and MDM2 expression in gastric cells in vitro. The expression of MDM2 on gastric biopsies was studied immunohistochemistry. AGS cells were incubated with a combination of IL-16 and Helicobacter pylori (H. pylori). Gastric epithelial cell proliferation was studied by BrdU uptake and the expressions of MDM2 were studied by ELISA. There was no significant difference on the expression of MDM2 between with and without H. pylori infected chronic gastritis. In H. pylori infected gastric mucosa; the MDM2 expression was higher on intestinal metaplasia and gastric cancer than chronic gastritis. IL-16 administration was increased MDM2 expression and cell proliferation on AGS cells, which was decreased by H. pylori infection. In conclusion, the expression of MDM2 in long-term H. pylori infected gastric mucosa may indicate a risk for carcinogenesis. IL-16 secretion in H. pylori infected mucosa is one of the factors for gastric cancer. The expression of MDM2 on mucosa can be a mediator for gastric cancer.
    Journal of Clinical Biochemistry and Nutrition 04/2009; 44(2):196-202. · 1.98 Impact Factor

Keywords

12 patients
 
31 patients
 
6 months
 
biopsy specimens
 
cell proliferation
 
Endoscopic biopsies
 
gastric antrum
 
gastric mucosa
 
H. pylori
 
H. pylori eradication
 
H. pylori infection
 
H. pylori-infected gastric mucosa
 
H. pylori-infected group
 
Helicobacter pylori
 
MDM2 levels
 
non-infected gastric mucosa
 
normal gastric mucosa
 
primary antibodies specific
 
successful eradication
 
tumor suppressor p53
 

Masaaki Kodama