The Expression of Murine Double Minute 2 (MDM2) on Helicobacter pylori-Infected Intestinal Metaplasia and Gastric Cancer

Abstract

Summary 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.

Helicobacter pylori: a ROS-inducing bacterial species in the stomach

“…The detailed mechanism has been recently reported with regard to murine double minute 2 (MDM2) which binds to the tumor suppressor p53 and inhibits p53-mediated transactivation. Nakajima et al [49] has found that MDM2 expression is higher in biopsy specimens of intestinal metaplasia and gastric cancer than that of chronic gastritis in H. pylori-infected stomach and that interleukin-16 (IL-16), a T-cell chemoattractant that has been shown to be involved in H. pylori-induced gastric inflammation, increased the expression of MDM2 and cell proliferation of a gastric cancer cell line. Since the overexpression of MDM2 has been shown in several human tumors, and increased expression of MDM2 inactivates the apoptotic and cell cycle arrest function of p53, the expression of MDM2 in long-term H. pylori-infected gastric mucosa may indicate a risk for carcinogenesis, and IL-16 secretion in H. pylori-infected mucosa is one of the factors for gastric carcinogenesis.…”

Mechanism Analyses for Elucidating the Role of LOXL2 Silencing in Hepatocellular Carcinoma

“…The expression of MDM2 is linked to gain-of-function mutations in many tumors [34]. In addition, the inhibition of MDM2 was shown to block tumor growth or induce cell apoptosis in a number of tumors [35][36][37][38][39]. In addition, DNA amplification of BIRC3 has been observed in mouse liver and human lung cancers, liver carcinoma, oral squamous cell carcinoma, medulloblastoma, glioblastoma and pancreatic cancer [40].…”

Expression and significance of p53 and mdm2 in atypical intestinal metaplasia and gastric carcinoma

“…Findings of previous studies have suggested that the expression of mdm2 increases in gastric carcinoma (36,37). Nakajima et al (3) reported that expression of the mdm2 protein increased not only in gastric cancer, but also in intestinal metaplasia as compared to chronic gastritis. A distinct mdm2 expression was observed in our study, indicating the precancerous nature of AIM more accurately than mucous classification.…”