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Promoter methylation down-regulates osteoprotegerin expression in ovarian carcinoma

Authors
 JI-YE KIM  ;  SE HOON KIM  ;  HYUN-SOO KIM 
Citation
 Anticancer Research, Vol.39(5) : 2361-2367, 2019 
Journal Title
 Anticancer Research 
ISSN
 0250-7005 
Issue Date
2019
MeSH
Biomarkers, Tumor/genetics ; Carcinogenesis/genetics ; Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/pathology ; Cell Line, Tumor ; DNA Methylation/genetics ; Epigenesis, Genetic/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Osteoprotegerin/genetics ; Promoter Regions, Genetic
Keywords
Ovarian carcinoma ; osteoprotegerin ; promoter methylation status
Abstract
BACKGROUND/AIM: Previous studies have documented that osteoprotegerin (OPG) is involved in the development and progression of several human malignancies. However, OPG has also been shown to act as a tumor suppressor. The aim of this study was to examine the expression status of OPG in ovarian carcinoma cells and investigate the underlying mechanism responsible for alterations in OPG expression. MATERIALS AND METHODS: The expression levels of OPG mRNA and protein were assessed in human ovarian carcinoma cell lines. The methylation status of the OPG promoter region was determined using the bisulfite pyrosequencing technique. The effects of demethylation on OPG expression were also analyzed. RESULTS: The human ovarian carcinoma cell lines, SW 626, OVCAR-3, ES-2, TOV-112D, and TOV-21G, expressed significantly lower levels of OPG mRNA and protein than the normal human ovarian epithelial cell line, HS823.Tc. Moreover, three CpG sites in the OPG promoter region were highly methylated in the SW 626, OVCAR-3, ES-2, and TOV-112D ovarian carcinoma cell lines compared to normal control cells. Furthermore, in all the examined ovarian carcinoma cell lines, treatment with the demethylating agent, 5-aza-2-deoxycytidine, resulted in significantly increased expression levels of OPG mRNA and protein compared to the respective pre-treatment levels. CONCLUSION: OPG expression was down-regulated in the studied ovarian carcinoma cells compared to the normal control cells, while demethylation significantly restored OPG expression in the OPG-down-regulated cell lines. Our results suggest that OPG down-regulation in ovarian carcinoma occurs, at least partly, through epigenetic repression, suggesting its involvement in ovarian carcinogenesis.
Full Text
http://ar.iiarjournals.org/content/39/5/2361.long
DOI
10.21873/anticanres.13353
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170276
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