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ID 52782
FullText URL
Author
Hayashi, Tatsuro
Toyooka, Shinichi
Shien, Tadahiko ORCID Kaken ID publons
Taira, Naruto Kaken ID
Maki, Yuho
Tanaka, Norimitsu
Doihara, Hiroyoshi Kaken ID researchmap
Miyoshi, Shinichiro Kaken ID publons researchmap
Abstract
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. 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. 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 non-methylated group. 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.
Keywords
DNA methylation
REIC/Dkk-3
Breast cancer
Lung cancer
Mesothelioma
Published Date
2012-05
Publication Title
Journal of Cancer Research and Clinical Oncology
Volume
volume138
Issue
issue5
Publisher
Springer
Start Page
799
End Page
809
ISSN
0171-5216
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52511
language
英語
File Version
author
Refereed
True
DOI
Web of Science KeyUT