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Downregulation of EphA7 by hypermethylation in colorectal cancer

Oncogene volume 24, pages 5637–5647 (2005)Cite this article

Abstract

A significant reduction of EphA7 expression in human colorectal cancers was shown using semiquantitative reverse transcription–polymerase chain reaction analysis in 59 colorectal cancer tissues, compared to corresponding normal mucosas (P=0.008), and five colon cancer cell lines. To investigate the mechanism of EphA7 downregulation in colorectal cancer, we examined the methylation status of the 5′CpG island around the translation start site in five colon cancer cell lines using restriction enzymes, methylation-specific PCR, and bisulfite sequencing and found evidence of aberrant methylation. The expression of EphA7 in colon cancer cell lines was restored after treatment with 5-aza-2′-deoxycytidine. Analysis of methylation status in totally 75 tumors compared to clinicopathological parameters revealed that hypermethylation of colorectal cancers was more frequent in male than in female (P=0.0078), and in moderately differentiated than in well-differentiated adenocarcinomas (P=0.0361). There was a tendency that hypermethylation in rectal cancers was more frequent than in colon cancers (P=0.0816). Hypermethylation was also observed in colorectal adenomas. This is the first report describing the downregulation of an Eph family gene in a solid tumor via aberrant 5′CpG island methylation. It provides the evidence that EphA7 gene is involved in human colorectal carcinogenesis.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

MSP:

methylation specific PCR

PCR:

polymerase chain reaction

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Acknowledgements

This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare for the Second-term Comprehensive 10-Year Strategy for Cancer Control, from the Smoking Research Foundation, and from the Ministry of Education, Culture, Sports, Science and Technology of Japan for Scientific Research on Priority Area and the 21st century COE program ‘Medical Photonics’. Wang JD is a Yoneyama Rotary Scholarship awardee.

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Author notes

  1. Masamitsu Tanaka

    Present address: Growth Factor Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0054, Japan

Authors and Affiliations

  1. Department of Pathology, Hamamatsu University School of Medicine, 1-20-1, Handayama, 431-3192, Hamamatsu, Japan

    Jiandong Wang, Hideki Kataoka, Masaya Suzuki, Ritsuko Nakamura, Hong Tao, Megumi Ihara, Masamitsu Tanaka, Kazuya Shinmura & Haruhiko Sugimura

  2. Department of Medicine, Hamamatsu University School of Medicine, 1-20-1, Handayama, 431-3192, Hamamatsu, Japan

    Hideki Kataoka & Shigeru Kanaoka

  3. Department of Clinical Nursing, Hamamatsu University School of Medicine, 1-20-1, Handayama, 431-3192, Hamamatsu, Japan

    Naomi Sato

  4. Department of Surgery, Hamamatsu University School of Medicine, 1-20-1, Handayama, 431-3192, Hamamatsu, Japan

    Keiji Maruyama, Jun Isogaki & Toshio Nakamura

  5. Department of Public Health of Hamamatsu University School of Medicine, 1-20-1, Handayama, 431-3192, Hamamatsu, Japan

    Masao Kanamori

  6. Department of Lifelong Sport, Biwako Seikei Sport College, 1204 Shigachou, Shigagun, 520-0503, Shiga, Japan

    Masao Kanamori

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  1. Jiandong Wang
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Correspondence to Haruhiko Sugimura.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Wang, J., Kataoka, H., Suzuki, M. et al. Downregulation of EphA7 by hypermethylation in colorectal cancer. Oncogene 24, 5637–5647 (2005). https://doi.org/10.1038/sj.onc.1208720

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