Downregulation of retinoic acid receptor-beta(2) expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines.
OBJECTIVE
To study the role of hypermethylation in the loss of retinoic acid receptor beta(2) (RARbeta(2)) in esophageal squamous cell carcinoma (ESCC).


METHODS
The role of hypermethylation in RARbeta(2) gene silencing in 6 ESCC cell lines was determined by methylation-specific PCR (MSP), and its methylation status was compared with RARbeta(2) mRNA expression by RT-PCR. The MSP results were confirmed by bisulfite sequencing of RARbeta(2) promoter regions.


RESULTS
Methylation was detected in 4 of the 6 cell lines, and the expression of RARbeta(2) was markedly downregulated in 3 of the 4 methylated cell lines. The expression of RARbeta(2) was restored in one RARbeta(2) -downregulated cell line with the partial demethylation of promoter region of RARbeta(2) after 5-aza-2'-deoxycytidine (5-aza-dc) treatment.


CONCLUSIONS
The methylation of the 5' region may play an important role in the downregulation of RARbeta(2) in some ESCC cell lines, suggesting that multiple mechanisms contribute to the loss of RARbeta(2) expression in ESCC cell lines. This study may have clinical applications for treatment and prevention of ESCC.
Liu
Zhong-Min
ZM
National Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. liuzh@pubem.cicams.ac.cn
Ding
Fang
F
Guo
Ming-Zhou
MZ
Zhang
Li-Yong
LY
Wu
Min
M
Liu
Zhi-Hua
ZH
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D019175:DNA Methylation; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*
D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta