p14ARF repression induced by promoter methylation associated with metastasis in esophageal squamous cell carcinoma

Abstract

Summary: The objective of this study is to evaluate the promoter methylation status of the p14ARF in esophageal squamous cell carcinoma (ESCC). Cell lines were treated with the demethylation agent 5-aza-2'-deoxycytidine, and p14ARF messenger RNA (mRNA) expression was detected by reverse transcription-polymerase chain reaction. We analyzed the methylation status of p14ARF promoter by methylation-specific polymerase chain reaction in 50 ESCC and their noncarcinoma tissues. Then demethylation caused by 5-aza-2'-deoxycytidine increased the p14ARF mRNA expression level in esophagus cancer cell lines. p14ARF methylation was found in 48% (24 of 50) of ESCC patients but only in 18% (9 of 50) corresponding noncarcinoma tissues (P = 0.001). There was a statistically significant correlation between the presence of methylation and tumor metastasis (P < 0.001). The p14ARF mRNA was lower in ESCC tissues than nontumor tissues (mean ± standard deviation, 0.47 ± 0.32 vs. 1.40 ± 0.58; P = 0.002). Meanwhile, a signification association was found between the methylation status of p14ARF promoter and p14ARF mRNA expression in tissues (P < 0.05). The aberrant promoter methylation of p14ARF is a common phenomenon in ESCC, which may be an important mechanism of downregulating p14ARF mRNA expression. © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.