title: Bile acid induces MUC2 expression and inhibits tumor invasion in gastric carcinomas.
abstract: OBJECTIVE
  Bile acids might induce mucin expression and regulate tumor behavior in esophageal and colon cancers. However, little is known about the effect of bile acids on tumor invasiveness of gastric carcinoma (GC). The aim of the current study was to elucidate the mechanisms by which bile acids regulate tumor invasion in GC.
  
  
  METHODS
  We investigated bile acid-induced MUC2 expression and cell invasion and migration in the cultured GC cell lines, SNU-216, and MKN45. In addition, immunohistochemical analysis of MUC2 and Snail was performed on 389 archival paraffin-embedded tissues of GC to evaluate the correlation of their expression with prognosis.
  
  
  RESULTS
  Deoxycholic acid (DCA), a secondary bile acid, had no effect on the viability of SNU-216 and MKN45 GC cells at low concentrations (0-100 μM), but decreased viability at a higher concentration (200 μM). MKN45 cells showed higher MUC2 expression than SNU-216 cells under basal conditions. DCA treatment upregulated MUC2 mRNA expression in both SNU-216 and MKN45 cells. Expression of Snail and MMP9 was markedly decreased by DCA treatment, and E-cadherin expression was subsequently increased. DCA significantly inhibited invasion and migration of SNU-216 and MKN45 cells. In human GC, MUC2 expression showed a negative correlation with Snail expression (P = 0.021) and a significantly positive correlation with better prognosis (P = 0.023).
  
  
  CONCLUSIONS
  Taken together, our data suggest that DCA induced MUC2 expression in GC cells and inhibited tumor invasion and migration. Additionally, MUC2-expressing GCs showed low rates of Snail expression and were associated with a favorable prognosis.
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 78 Saemunan-gil, Jongno-gu, Seoul, 110-746, South Korea.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Pyo
authors.forename: Young San
authors.initials: YS
authors.lastname: Ko
authors.forename: Guhyun
authors.initials: G
authors.lastname: Kang
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Sohn
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D001647:Bile Acids and Salts / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D003840:Deoxycholic Acid / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D055262:Mucin-2 / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D001647:Bile Acids and Salts; D014408:Biomarkers, Tumor; C524625:MUC2 protein, human; D055262:Mucin-2; D003840:Deoxycholic Acid