Molecular mechanism of human stomach carcinogenesis implicated in Helicobacter pylori infection.
Genetic and epigenetic alterations in oncogenes, tumor suppressor genes, cell adhesion molecules, telomere and telomerase activity as well as genetic instability at several microsatellite foci are responsible for multistep process of human stomach carcinogenesis. The scenario of these alterations found in gastric cancer differs depending on the two histological types, indicating that different genetic pathways exist for well differentiated or intestinal type and poorly differentiated or diffuse type gastric cancers, even though both types of gastric cancer may arise from epithelial "stem cells" which express human telomerase reverse transcriptase (hTRT) and telomerase activity. Infection with Helicobacter pylori, which evidently causes the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS), may be a strong trigger for "stem cell" hyperplasia in intestinal metaplasia, followed by telomere reduction and increase telomerase activity as well as hTRT overexpression. They may precede DNA replication error, DNA hypermethylation, CD44 abnormal transcript and p53 mutations, all of which occur in at least 30% of intestinal metaplasia as early events of multistep pathogenesis of well differentiated type gastric cancer.
Tahara
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First Department of Pathology, Hiroshima University School of Medicine, Japan.
D004273:DNA, Neoplasm / Q000235:genetics; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D006965:Hyperplasia; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004273:DNA, Neoplasm; D018960:Hyaluronan Receptors; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D019098:Telomerase