title: Helicobacter pylori activates the proto-oncogene c-fos through SRE transactivation.
abstract: Epidemiological studies have demonstrated a strong association between Helicobacter pylori infection and gastric cancer. However, there have been few detailed studies on the mechanism of cellular proliferation by H. pylori. Thus, we examined activation of the proto-oncogene c-fos to elucidate the underlying mechanism of cell proliferation caused by H. pylori. Activation of c-fos was evaluated in human gastric cancer cells (TMK1) by Northern blot and reporter assays with deletion analysis of the c-fos transcriptional control region. c-fos promoter activation and transcription were enhanced when cocultured with cag-positive strains. H. pylori-mediated c-fos promoter activation was inhibited by MEK1/2 inhibitor (U0126). The deletion analysis indicated that serum response element (SRE) was required for the activation of c-fos by H. pylori. In conclusion, c-fos promoter activation and transcription were enhanced through the activation of extracellular signal-regulated kinases (ERK)/mitogen-activated protein kinase (MAPK) cascade in gastric cancer cells when cocultured with H. pylori possessing intact cag PAI. SRE is required for the activation of c-fos by H. pylori. These results suggest a direct involvement of H. pylori infection in cellular proliferation, which may play a role in neoplastic transformation.
authors.affiliation: Department of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. MITSUNO-21M@h.u-tokyo.ac.jp
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Mitsuno
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Keiji
authors.initials: K
authors.lastname: Ogura
authors.forename: Masao
authors.initials: M
authors.lastname: Akanuma
authors.forename: Takao
authors.initials: T
authors.lastname: Kawabe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D000328:Adult; D000368:Aged; D002070:Butadienes / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017384:Sequence Deletion; D027602:Serum Response Element; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; C000715470:MAS1 protein, human; D009570:Nitriles; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D012334:RNA, Neoplasm; C113580:U 0126; D020929:Mitogen-Activated Protein Kinase Kinases