title: Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells.
abstract: BACKGROUND
  The hypermethylation of Alcohol dehydrogenase iron containing 1 (ADHFE1) was recently reported to be associated with colorectal cancer (CRC) differentiation. However, the effect of alcohol on ADHFE1 hypermethylation in CRC is still unclear.
  
  
  METHODS
  The methylation status and expression levels of ADHFE1 were investigated in primary tumor tissues and adjacent normal tissues of 73 patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29, SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain reaction (QMSP) and real-time reverse transcription polymerase chain reaction (real time PCR), respectively. The effect of alcohol on the methylation status of ADHFE1 was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real-time PCR, immunoblot, and cell proliferation assay.
  
  
  RESULTS
  ADHFE1 was hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues (p<0.05). The mRNA expression of ADHFE1 was significantly reduced in CRC compared to adjacent normal tissues (p<0.05) and its expression was decreased in the alcohol consumption group (p<0.05). ADHFE1 was hypermethylated and its expression was decreased in 4 CRC cell lines compared with normal colon cell line. Alcohol induced hypermethylation of ADHFE1, decreased its expression, and stimulated cell proliferation of HT-29, SW480, and DLD-1cells.
  
  
  CONCLUSIONS
  These results demonstrate that the promoter hypermethylation of ADHFE1 is frequently present in CRC and alcohol induces methylation-mediated down expression of ADHFE1 and proliferation of CRC cells.
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jung Seon
authors.initials: JS
authors.lastname: Seo
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Institute of Human Genetics, Department of Anatomy, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Republic of Korea. parksh@korea.ac.kr.
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Park
mesh_terms: D000429:Alcohol Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D000438:Alcohols / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects
chemical_list: D000438:Alcohols; D024101:Mitochondrial Proteins; D000429:Alcohol Oxidoreductases; C072878:hydroxyacid-oxoacid transhydrogenase