title: Deoxycholic acid induces the overexpression of intestinal mucin, MUC2, via NF-kB signaling pathway in human esophageal adenocarcinoma cells.
abstract: BACKGROUND
  Mucin alterations are a common feature of esophageal neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the esophagus. Bile acids have been linked to esophageal adenocarcinoma and mucin secretion, but their effects on mucin gene expression in human esophageal adenocarcinoma cells is unknown.
  
  
  METHODS
  Human esophageal adenocarcinoma cells were treated 18 hours with 50-300 muM deoxycholic acid, chenodeoxycholic acid, or taurocholic acid. MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct and MUC2 protein was assayed by Western blot analysis. Transcription Nuclear factor-kappaB activity was measured using a Nuclear factor-kappaB reporter construct and confirmed by Western blot analysis for Nuclear factor-kappaB p65.
  
  
  RESULTS
  MUC2 transcription and MUC2 protein expression were increased four to five fold by bile acids in a time and dose-dependent manner with no effect on cell viability. Nuclear factor-kappaB activity was also increased. Treatment with the putative chemopreventive agent aspirin, which decreased Nuclear factor-kappaB activity, also decreased MUC2 transcription. Nuclear factor-kappaB p65 siRNA decreased MUC2 transcription, confirming the significance of Nuclear factor-kappaB in MUC2 induction by deoxycholic acid. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid induced MUC2 transcription and Nuclear factor-kappaB activity, whereas inhibitors of MAP kinase had no effect.
  
  
  CONCLUSIONS
  Deoxycholic acid induced MUC2 overexpression in human esophageal adenocarcinoma cells by activation of Nuclear factor-kappaB transcription through a process involving PKC-dependent but not PKA, independent of activation of MAP kinase.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710004, PR China. wujjtt@gmail.com
authors.forename: Jiantao
authors.initials: J
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.forename: Juan
authors.initials: J
authors.lastname: Geng
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Song
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D001241:Aspirin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005765:Gastrointestinal Agents / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D055262:Mucin-2 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D013656:Taurocholic Acid / Q000494:pharmacology
chemical_list: D002756:Cholagogues and Choleretics; D005765:Gastrointestinal Agents; C524625:MUC2 protein, human; D055262:Mucin-2; D016328:NF-kappa B; D009281:Naphthalenes; D034741:RNA, Small Interfering; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D013656:Taurocholic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C058819:calphostin C; D001241:Aspirin