title: Downregulation of gastrokine-1 in gastric cancer tissues and restoration of its expression induced gastric cancer cells to apoptosis.
abstract: BACKGROUND
  Gastrokine-1 (GKN1), a secreted protein, is specifically expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The present study investigated differential expression of GKN1 in normal, precancerous, and cancerous gastric tissues, and explored the biological functions of GKN1 protein in gastric cancer cells.
  
  
  METHODS
  RT-PCR, Western blot, and immunohistochemistry were performed to detect GKN1 expression in normal, precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene transfection was used to restore GKN1 expression in gastric cancer AGS cells. Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the transfected cells. DNA microarrays were used to analyze expression changes of apoptosis-related genes.
  
  
  RESULTS
  Significant downregulation or absence of GKN1 expression in seven gastric cancer cell lines were detected and progressive decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related genes.
  
  
  CONCLUSIONS
  Expression of GKN1 is progressively lost from normal mucosa, precancerous to cancerous gastric tissues, while restoration of GKN1 expression induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of gastric cancer cells to 5-FU-induced apoptosis.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Mao
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Tie-Li
authors.initials: TL
authors.lastname: Peng
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Yin
authors.forename: Lian-Zhou
authors.initials: LZ
authors.lastname: Chen
authors.forename: Min-Hu
authors.initials: MH
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C477000:GKN1 protein, human; D036361:Peptide Hormones; D005472:Fluorouracil