Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines
Abstract
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.
Journal
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- International Journal of Oncology
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International Journal of Oncology 25 (5), 1415-1421, 2004-11
Spandidos Publications
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Keywords
Details 詳細情報について
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- CRID
- 1050282813982498944
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- NII Article ID
- 120002004297
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- HANDLE
- 2115/42834
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles