title: Silence of HIN-1 expression through methylation of its gene promoter in gastric cancer.
abstract: OBJECTIVE
  To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development.
  
  
  METHODS
  Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and protein using the semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The methylation of the HIN-1 gene promoter was detected in gastric carcinoma cells and tissues using methylation-specific polymerase chain reaction. The 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay and flow cytometry were used to assess the changes in behaviors of gastric cancer cells with or without 5-aza-2'-deoxycytidine treatment.
  
  
  RESULTS
  HIN-1 was not expressed in 4 of 5 gastric cancer cell lines. The demethylation reagent 5-aza-2'-deoxycytidine was able to induce or upregulate HIN-1 expression in gastric cancer cell lines, which is associated with reduction of tumor cell viability. Furthermore, methylation of the HIN-1 gene promoter was shown in 57.8% (26/45) of the primary gastric cancer and 42.1% (17/38) of adjacent tissue samples, but was not shown in normal gastric mucosa (0/10). From the clinicopathological data of the patients, methylation of the HIN-1 gene promoter was found to be associated with tumor differentiation (P = 0.000).
  
  
  CONCLUSIONS
  High methylation of HIN-1 gene promoter results in silence of HIN-1 expression in gastric cancer. 5-aza-2'-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells.
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Ming-Zhou
authors.initials: MZ
authors.lastname: Guo
authors.forename: Zhi-Jia
authors.initials: ZJ
authors.lastname: Ye
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Zhang
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Zhao
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Yang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; C434732:SCGB3A1 protein, human; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine