Kyu Kwang Kim1, Han Bok Kim. 1. Department of Biotechnology, The Research Institute for Basic Sciences, Hoseo University, Asan 336-795, South Korea. hbkim@hoseo.edu.
Abstract
AIM: To understand the complex reaction of gastric inflammation induced by Helicobacter pylori (H pylori) in a systematic manner using a protein interaction network. METHODS: The expression of genes significantly changed on microarray during H pylori infection was scanned from the web literary database and translated into proteins. A network of protein interactions was constructed by searching the primary interactions of selected proteins. The constructed network was mathematically analyzed and its biological function was examined. In addition, the nodes on the network were checked to determine if they had any further functional importance or relation to other proteins by extending them. RESULTS: The scale-free network showing the relationship between inflammation and carcinogenesis was constructed. Mathematical analysis showed hub and bottleneck proteins, and these proteins were mostly related to immune response. The network contained pathways and proteins related to H pylori infection, such as the JAK-STAT pathway triggered by interleukins. Activation of nuclear factor (NF)-kappaB, TLR4, and other proteins known to function as core proteins of immune response were also found. These immune-related proteins interacted on the network with pathways and proteins related to the cell cycle, cell maintenance and proliferation, and transcription regulators such as BRCA1, FOS, REL, and zinc finger proteins. The extension of nodes showed interactions of the immune proteins with cancer-related proteins. One extended network, the core network, a summarized form of the extended network, and cell pathway model were constructed. CONCLUSION: Immune-related proteins activated by H pylori infection interact with proto-oncogene proteins. The hub and bottleneck proteins are potential drug targets for gastric inflammation and cancer.
AIM: To understand the complex reaction of gastric inflammation induced by Helicobacter pylori (H pylori) in a systematic manner using a protein interaction network. METHODS: The expression of genes significantly changed on microarray during H pylori infection was scanned from the web literary database and translated into proteins. A network of protein interactions was constructed by searching the primary interactions of selected proteins. The constructed network was mathematically analyzed and its biological function was examined. In addition, the nodes on the network were checked to determine if they had any further functional importance or relation to other proteins by extending them. RESULTS: The scale-free network showing the relationship between inflammation and carcinogenesis was constructed. Mathematical analysis showed hub and bottleneck proteins, and these proteins were mostly related to immune response. The network contained pathways and proteins related to H pylori infection, such as the JAK-STAT pathway triggered by interleukins. Activation of nuclear factor (NF)-kappaB, TLR4, and other proteins known to function as core proteins of immune response were also found. These immune-related proteins interacted on the network with pathways and proteins related to the cell cycle, cell maintenance and proliferation, and transcription regulators such as BRCA1, FOS, REL, and zinc finger proteins. The extension of nodes showed interactions of the immune proteins with cancer-related proteins. One extended network, the core network, a summarized form of the extended network, and cell pathway model were constructed. CONCLUSION: Immune-related proteins activated by H pylori infection interact with proto-oncogene proteins. The hub and bottleneck proteins are potential drug targets for gastric inflammation and cancer.
Authors: C Prinz; M Schöniger; R Rad; I Becker; E Keiditsch; S Wagenpfeil; M Classen; T Rösch; W Schepp; M Gerhard Journal: Cancer Res Date: 2001-03-01 Impact factor: 12.701
Authors: N J Talley; A R Zinsmeister; A Weaver; E P DiMagno; H A Carpenter; G I Perez-Perez; M J Blaser Journal: J Natl Cancer Inst Date: 1991-12-04 Impact factor: 13.506
Authors: Véronique J Hofman; Chimène Moreilhon; Patrick D Brest; Sandra Lassalle; Kevin Le Brigand; Dominique Sicard; Josette Raymond; Dominique Lamarque; Xavier A Hébuterne; Bernard Mari; Pascal Jp Barbry; Paul M Hofman Journal: Mod Pathol Date: 2007-07-20 Impact factor: 7.842