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Epigenetic inactivation of E-cadherin by promoter hypermethylation in oral carcinoma cells

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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.

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Authors and Affiliations

  1. Department of Biochemistry, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan

    Genta Maeda, Tadashige Chiba & Kazushi Imai

  2. Department of Pathology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan

    Takaaki Aoba

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  1. Genta Maeda
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  2. Tadashige Chiba
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  3. Takaaki Aoba
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  4. Kazushi Imai
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Correspondence to Kazushi Imai.

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Maeda, G., Chiba, T., Aoba, T. et al. Epigenetic inactivation of E-cadherin by promoter hypermethylation in oral carcinoma cells. Odontology 95, 24–29 (2007). https://doi.org/10.1007/s10266-007-0068-6

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  • DOI: https://doi.org/10.1007/s10266-007-0068-6

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