start-ver=1.4
cd-journal=joma
no-vol=138
cd-vols=
no-issue=5
article-no=
start-page=799
end-page=809
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201205
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=DNA methylation status of REIC/Dkk-3 gene in human malignancies
en-subtitle=
kn-subtitle=
en-abstract=
kn-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.
en-copyright=
kn-copyright=

en-aut-name=HayashiTatsuro
en-aut-sei=Hayashi
en-aut-mei=Tatsuro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AsanoHiroaki
en-aut-sei=Asano
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TsukudaKazunori
en-aut-sei=Tsukuda
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShienTadahiko
en-aut-sei=Shien
en-aut-mei=Tadahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=TairaNaruto
en-aut-sei=Taira
en-aut-mei=Naruto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MakiYuho
en-aut-sei=Maki
en-aut-mei=Yuho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=TanakaNorimitsu
en-aut-sei=Tanaka
en-aut-mei=Norimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=DoiharaHiroyoshi
en-aut-sei=Doihara
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=NasuYasutomo
en-aut-sei=Nasu
en-aut-mei=Yasutomo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=HuhNam-ho
en-aut-sei=Huh
en-aut-mei=Nam-ho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MiyoshiShinichiro
en-aut-sei=Miyoshi
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg

affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Urol

affil-num=12
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol

affil-num=13
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg
en-keyword=DNA methylation
kn-keyword=DNA methylation
en-keyword=REIC/Dkk-3
kn-keyword=REIC/Dkk-3
en-keyword=Breast cancer
kn-keyword=Breast cancer
en-keyword=Lung cancer
kn-keyword=Lung cancer
en-keyword=Mesothelioma
kn-keyword=Mesothelioma
END