Liu ZM, Ding F, Guo MZ, Zhang LY, Wu M, Liu ZH. Downregulation of retinoic acid receptor-β2 expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines. World J Gastroenterol 2004; 10(6): 771-775 [PMID: 15040015 DOI: 10.3748/wjg.v10.i6.771]
Corresponding Author of This Article
Zhi-Hua Liu, Professor, National Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China. liuzh@pubem.cicams.ac.cn
Article-Type of This Article
Esophageal Cancer
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World J Gastroenterol. Mar 15, 2004; 10(6): 771-775 Published online Mar 15, 2004. doi: 10.3748/wjg.v10.i6.771
Downregulation of retinoic acid receptor-β2 expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines
Zhong-Min Liu, Fang Ding, Ming-Zhou Guo, Li-Yong Zhang, Min Wu, Zhi-Hua Liu
Zhong-Min Liu, Fang Ding, Li-Yong Zhang, Min Wu, Zhi-Hua Liu, National Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
Ming-Zhou Guo, Division of Tumor Biology, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
Author contributions: All authors contributed equally to the work.
Supported by China Key Program on Basic Research, G1998051021, the Chinese Hi-tech R&D program, 2001AA231041, and National Science Foundation of China, 30170519
Correspondence to: Zhi-Hua Liu, Professor, National Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China. liuzh@pubem.cicams.ac.cn
Telephone: +86-10-67723789 Fax: +86-10-67723789
Received: December 10, 2003 Revised: January 3, 2004 Accepted: January 8, 2004 Published online: March 15, 2004
Abstract
AIM: To study the role of hypermethylation in the loss of retinoic acid receptor β2 (RARβ2) in esophageal squamous cell carcinoma (ESCC).
METHODS: The role of hypermethylation in RARβ2 gene silencing in 6 ESCC cell lines was determined by methylation-specific PCR (MSP), and its methylation status was compared with RARβ2 mRNA expression by RT-PCR. The MSP results were confirmed by bisulfite sequencing of RARβ2 promoter regions.
RESULTS: Methylation was detected in 4 of the 6 cell lines, and the expression of RARβ2 was markedly downregulated in 3 of the 4 methylated cell lines. The expression of RARβ2 was restored in one RARβ2 -downregulated cell line with the partial demethylation of promoter region of RARβ2 after 5-aza-2’-deoxycytidine (5-aza-dc) treatment.
CONCLUSION: The methylation of the 5’ region may play an important role in the downregulation of RARβ2 in some ESCC cell lines, suggesting that multiple mechanisms contribute to the loss of RARβ2 expression in ESCC cell lines. This study may have clinical applications for treatment and prevention of ESCC.