Hypermethylation-Associated Inactivation of Retinoic Acid Receptor β in Human Esophageal Squamous Cell Carcinoma

Yimin Wang, Ming Zhu Fang, Jie Liao, Guang Yu Yang, Yan Nie, Yunlong Song, Chi So, Xiaochun Xu, Li Dong Wang, Chung S. Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Purpose: The purpose of this study was to investigate the mechanism of altered retinoic acid receptor β (RARβ) expression during esophageal squamous carcinogenesis. Experimental Design: Samples were collected from Linzhou, China. The hypermethylation of CpG islands in the promoter region of the RARβ gene was examined by methylation-specific PCR in human esophageal squamous cell carcinoma (ESCC) samples, as well as in neighboring tissues with normal epithelium, basal cell hyperplasia, and dysplasia. RARβ mRNA expression was determined by in situ hybridization. The DNA methyltransferase inhibitor 2′-deoxy-5-azacytidine was used to treat the ESCC cell line, and the DNA hypermethylation status and mRNA expression level were examined. Results: Two of 17 (12%) normal, 9 of 21 basal cell hyperplasia (43%), 7 of 12 dysplasia (58%), and 14 of 20 ESCC (70%) samples had hypermethylation of the RARβ promoter region. The loss of RARβ mRNA expression was highly concordant with RARβ promoter CpG island hypermethylation when individual samples were considered in the correlation analysis. Good statistical correlation between hypermethylation and loss of RARβ expression was revealed. Frequencies of hypermethylation appeared to increase with the progression of carcinogenesis. In samples from the same patients, if hypermethylation was detected in earlier lesions, it was usually observed in more severe lesions. In the ESCC cell line KYSE 510, 2′ -deoxy-5-azacytidine partially reversed CpG island hypermethylation and restored RARβ mRNA expression. Conclusions: The results suggest that hypermethylation of RARβ promoter region is an important mechanism for RARβ gene silencing in esophageal squamous carcinogenesis.

Original languageEnglish (US)
Pages (from-to)5257-5263
Number of pages7
JournalClinical Cancer Research
Issue number14
StatePublished - Nov 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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