Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines
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概要
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The degree of E- and P-cadherin expressions inversely correlate with the progression stage of human melanoma. In the present study, we analyzed mechanisms of down-regulation of E- and P-cadherin gene expressions in 8 human melanoma cell lines. In 5 of the 8 melanoma cell lines, E-cadherin expression was lost or markedly decreased compared to that in normal melanocytes, and 4 of the 5 melanoma cell lines lost P-cadherin expression. All of the melanoma cell lines expressed snail, which is known to encode a transcription repressor for E-cadherin, at a higher level than melanocytes whereas expression levels of the snail varied among cell lines. Transduction of snail gene into MMAc cells which expressed a high level of E-cadherin and an extremely low level of snail decreased expression of E-cadherin but not P-cadherin. In contrast, transduction of antisense-snail gene into A375M cells which expressed no E-cadherin and a high level of snail restored expression of E-cadherin but not P-cadherin. Methylation-specific PCR analysis revealed CpG methylation in the promoter region of E-cadherin of MeWo and AKI cells. Further, the treatment with a demethylating agent, 5-azacytidine led AKI and A375M cells to re-express both E- and P-cadherin. The results show E-cadherin gene is silenced by at least two distinct mechanisms (methylation and transrepression by Snail) in human melanoma cell lines whereas P-cadherin gene seems to be silenced by methylation but not by snail.
- Spandidos Publicationsの論文
著者
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Tada Mitsuhiro
Division Of Cancer-related Genes Institute For Genetic Medicine Hokkaido University
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Moriuchi Tetsuya
Hokkaido Urothelial Cancer Research Group
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Moriuchi Tetsuya
Department Of Cell Biology Tokai University School Of Medicine
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Moriuchi Tetsuya
Division Of Cancer-related Genes Institute For Genetic Medicine Hokkaido University
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Yamamoto Yuhei
Department Of Plastic Surgery Hokkaido University Graduate School Of Medicine
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Tsutsumida Arata
Department Of Skin Oncology International Medical Center Saitama Medical University
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Yamamoto Yuhei
Department Of Plastic And Reconstructive Surgery Graduate School Of Medicine Hokkaido University
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