DNA methylation status of REIC/Dkk-3 gene in human malignancies

Tatsuro Hayashi, Hiroaki Asano, Shinichi Toyooka, Kazunori Tsukuda, Junichi Sou, Tadahiko Shien, Naruto Taira, Yuho Maki, Norimitsu Tanaka, Hiroyoshi Doihara, Yasutomo Nasu, Nam Ho Huh, Shinichiro Miyoshi

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Purpose: The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/ Dkk-3 type-a in a broad range of human malignancies. Methods: We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed. Results: The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the nonmethylated group. Conclusions: REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies.

Original languageEnglish
Pages (from-to)799-809
Number of pages11
JournalJournal of cancer research and clinical oncology
Issue number5
Publication statusPublished - May 2012


  • Breast cancer
  • DNA methylation
  • Lung cancer
  • Mesothelioma
  • REIC/Dkk-3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'DNA methylation status of REIC/Dkk-3 gene in human malignancies'. Together they form a unique fingerprint.

Cite this