Molecular mechanisms of H. pylori associated gastric carcinogenesis.

Abstract

Many molecules are involved in H. pylori associated gastric carcinogenesis. However, how the organism and its associated inflammation, interact with these molecules in gastric mucosa to induce carcinogenesis is still unknown. Over many years, H. pylori infected mucosa may experience sequential exposure to “damage-regeneration” (Figure ​(Figure1).1). Following the long-standing repeated damage-regenerate cycle, gastric atrophy and intestinal metaplasia gradually develop, which finally results in adenocarcinoma. During this process, the loss of p53 function may play an important role. As mentioned above, H. pylori infection may cause deficiency of p53 function and subsequently, this may not only lead to defects in the DNA damage-p53 mediated protective pathway, but the mutated p53 protein may also provide a possible selective advantage for tumor cell proliferation by attenuating apoptosis[71]. Furthermore, H. pylori infection has been shown to induce the reactivation of telomerase and to cause telomere dysfunction, which may cooperate with p53 deficiency to accelerate carcinogenesis[67]. In early stages of H. pylori infection, CD95 and bax mediated apoptosis may play an important role in eliminating damaged DNA or gene mutated cells, thereby maintaining genetic stability. However, H. pylori infection induces CD95L expression, which may suppress host immune responses by causing immunocyte apoptosis. Therefore, as shown in Figure ​Figure2,2, the loss of p53 function, reactivation of telomerase activity, inhibition of host immune responses, together with host genetic factors, may play important roles in the development of H. pylori associated carcinogenesis. Figure 1 Long-term H. pylori infection may induce a repeated “damage-regeneration” process which gradually leads to gastric atrophy, intestinal metaplasia and finally carcinoma. A. H. pylori infected gastric mucosa with inflammatory cell infiltration. ... Figure 2 Possible molecular mechanisms of H. pylori associated carcinogenesis. H. pylori and its associated inflammatory responses cause reactivation of telomerase, the loss of p53 function and also induce CD95 and bax mediated apoptosis. CD95L produced by gastric ... Footnotes Edited by Ma JY