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Open Access Highly Accessed Research article

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

Ji Wook Moon1, Soo Kyung Lee1, Yong Woo Lee1, Jung Ok Lee1, Nami Kim1, Hye Jeong Lee1, Jung Seon Seo1, Jin Kim2, Hyeon Soo Kim1 and Sun-Hwa Park1*

Author Affiliations

1 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

2 Department of General Surgery, Korea University Medical Center, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Republic of Korea

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BMC Cancer 2014, 14:377  doi:10.1186/1471-2407-14-377

Published: 28 May 2014

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.

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.

Keywords:
ADHFE1; Colorectal cancer; Hypermethylation; Alcohol; Quantitative methylation-specific polymerase chain reaction