Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells

作者：Moon Ji Wook; Lee Soo Kyung; Lee Yong Woo; Lee Jung Ok; Kim Nami; Lee Hye Jeong; Seo Jung Seon; Kim Jin; Kim Hyeon Soo; Park Sun Hwa^*

来源：BMC Cancer, 2014, 14(1): 377.

DOI：10.1186/1471-2407-14-377

• ADHFE1
• Colorectal cancer
• Hypermethylation
• Alcohol
• Quantitative methylation-specific polymerase chain reaction

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.
Conclusion: 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.

• 出版日期2014-5-28