RRC ID 43060
著者 Maeda G, Chiba T, Aoba T, Imai K.
タイトル Epigenetic inactivation of E-cadherin by promoter hypermethylation in oral carcinoma cells.
ジャーナル Odontology
Abstract The loss of E-cadherin expression by epigenetic aberrations, including promoter hypermethylation and transcription repressor binding, plays a key role in the initiation of the epithelial-mesenchymal transition, which leads to the progression of oral squamous cell carcinomas. However, mutual actions and roles of the epigenetic pathways remain to be elucidated. In this study, we determined the methylation status of cytosine within CpG islands of the E-cadherin promoter region in relation to the expression level of SIP1, a major E-cadherin repressor in oral carcinoma cells. Methylation-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analyses showed that the expression of E-cadherin was downregulated in parallel with promoter hypermethylation. The use of a bisulfite-modified sequence further validated that methylation was observed in 22.6 +/- 38.7% (mean +/- 1 SD) of cytosines in carcinoma cells negligibly expressing E-cadherin, in contrast to 7.5 +/- 1.8% in E-cadherin-expressing cells. Treatment with a demethylating reagent, 5-azacytidine, induced upregulation of E-cadherin in some E-cadherin-expressing carcinoma cell lines but not in others. The finding that the unresponsive cell lines retained high expression of SIP1 supports the repressive effect of SIP1 on E-cadherin expression regardless of promoter hypermethylation. Collectively, the overall results suggest the dynamic but differential regulation of E-cadherin by epigenetic aberrations in the pathology of oral carcinomas.
巻・号 95(1)
ページ 24-9
公開日 2007-7-1
DOI 10.1007/s10266-007-0068-6
PMID 17660978
MeSH Cadherins / antagonists & inhibitors Cadherins / biosynthesis Cadherins / genetics* Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism Cell Line, Tumor CpG Islands / physiology Cytosine / metabolism DNA Methylation Gene Expression Regulation, Neoplastic* Gene Silencing Humans Mouth Neoplasms / genetics* Mouth Neoplasms / metabolism Nerve Tissue Proteins / metabolism Promoter Regions, Genetic / physiology* RNA-Binding Proteins / metabolism Tumor Suppressor Proteins / antagonists & inhibitors Tumor Suppressor Proteins / biosynthesis Tumor Suppressor Proteins / genetics
IF 1.84
引用数 18
WOS 分野 DENTISTRY, ORAL SURGERY & MEDICINE
リソース情報
ヒト・動物細胞