Downregulation of retinoic acid receptor-βz expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines

AIM.To study the role of hypermethylation in the loss ofretinoic acid receptor β2(RARβ2) in esophageal squamouscell carcinoma (ESCC).METHODS:The role of hypermethylation in RARβ2genesilencing in 6 ESCC cell lines was determined by methylation-specific PCR (MSP),and its methylation status was comparedwith RARβ2mRNA expression by RT-PCR.The MSP resultswere confirmed by bisulfite sequencing of RARβ2promoterregions.RESULTS:Methylation was detected in 4 of the 6 cell lines,and the expression of RARβ2was markedly downregulatedin 3 of the 4 methylated cell lines.The expression of RARβ2was restored in one RARβ2-downregulated cell line with thepartial demethylation of promoter region of RARβ2after 5-aza-2’-deoxycytidine (5-aza-dc) treatment.CONCLUSION:The methylation of the 5’ region may playan important role in the downregulation of RARβ2in someESCC cell lines,suggesting that multiple mechanismscontribute to the loss of RARβ2expression in ESCC cell lines.This study may have clinical applications for treatment andprevention of ESCC.