title: Human gastrin mRNA expression up-regulated by Helicobacter pylori CagA through MEK/ERK and JAK2-signaling pathways in gastric cancer cells.
abstract: BACKGROUND
  Helicobacter pylori-cytotoxin-associated protein A (CagA) and gastrin are believed to play an important role in gastric carcinogenesis, but their interaction has been incompletely clear.
  
  
  METHODS
  We constructed a eukaryotic expression vector pcDNA3.1/cagA and a luciferase reporter vector pGL/gastrin promoter, and then co-transfected them into gastric cancer AGS and SGC-7901 cells. The two kinds of gastric cancer cells were, respectively, infected with cagA-positive H. pylori NCTC11637, and then the gastrin promoter activity and gastrin mRNA level were detected with a Dual-Luciferase reporter assay system and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Next, after the MEK/ERK and JAK2-signaling pathway inhibitors, U0126 and AG490, were used to treat the two cell lines, or the ERK1 and JAK2 genes were knocked down by siRNAs (small interference RNAs) in the two cell lines, the gastrin promoter activity and gastrin mRNA level were observed again.
  
  
  RESULTS
  The results indicated that CagA could activate the gastrin promoter and up-regulate gastrin mRNA expression in AGS and SGC-7901 cells, but these effects could be inhibited by the inhibitors U0126 and AG490, and the CagA-induced gastrin mRNA expression was down-regulated in the cells whose ERK1 or JAK2 gene was knocked down.
  
  
  CONCLUSIONS
  Gastrin promoter may be the transcriptional target of CagA, and CagA activates the gastrin promoter to up-regulate gastrin mRNA expression through the MEK/ERK and JAK1-signaling pathway in gastric cancer cells.
authors.affiliation: Affiliated Hospital, Guiyang Medical University, No. 9 Beijiang Road, Guiyang, China. gaochunyan1954@163.com
authors.forename: Jianjiang
authors.initials: J
authors.lastname: Zhou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002070:Butadienes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005755:Gastrins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002070:Butadienes; D004791:Enzyme Inhibitors; D005755:Gastrins; D009570:Nitriles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020032:Tyrphostins; C113580:U 0126; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C080866:cagA protein, Helicobacter pylori; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D048052:Mitogen-Activated Protein Kinase 3