title: Helicobacter pylori induction of the gastrin promoter through GC-rich DNA elements.
abstract: BACKGROUND
  Helicobacter pylori (H. pylori) infection has been linked to the development of chronic gastritis, duodenal ulcer disease, and gastric cancer. Helicobacter pylori- infected patients and animal models develop hypergastrinemia, chronic gastritis, and gastric atrophy. Since gastrin is an important regulator of gastric acid secretion and cell growth, H. pylori regulation of this hormone has been implicated in its pathogenesis.
  
  
  OBJECTIVE
  To investigate the effect of H. pylori on gastrin gene expression in mice and of human bacterial isolates on gastrin mRNA expressed in a human cell line.
  
  
  METHODS
  Gastrin mRNA was measured by qRT-PCR in H. pylori-infected mice. H. pylori were co-cultured with AGS cells to study regulation of human gastrin gene expression. Various MAP kinases were implicated in signal transduction from the bacteria using specific inhibitors. Gastrin reporter constructs and gel shift assays were used to map DNA responsive elements.
  
  
  RESULTS
  In addition to an increase in gastrin mRNA in H. pylori-infected mice, H. pylori induced the endogenous human gastrin gene through MAP kinase-dependent signaling but not NFκB-dependent signaling. Activation of gastrin through MAPK signaling did not require CagA or VacA virulence factors. Transfection studies demonstrated that a GC-rich motif mediated H. pylori-induction of the gastrin promoter and that the motif inducibly binds Sp1 and Sp3 transcription factors.
  
  
  CONCLUSIONS
  Direct contact of live H. pylori bacteria with human cells is sufficient to induce gastrin gene expression.
authors.affiliation: Departments of Internal Medicine, Microbiology and Immunology and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-2200, USA.
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Tucker
authors.forename: Brian M
authors.initials: BM
authors.lastname: Gray
authors.forename: Kathyrn A
authors.initials: KA
authors.lastname: Eaton
authors.forename: Juanita L
authors.initials: JL
authors.lastname: Merchant
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005755:Gastrins / Q000096:biosynthesis*; D015870:Gene Expression; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005755:Gastrins; D012333:RNA, Messenger