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Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines
| Title: | Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines |
| Authors: | Tsutsumida, Arata Browse this author | | Hamada, Jun-Ichi Browse this author | | Tada, Mitsuhiro Browse this author | | Aoyama, Tetsuya Browse this author | | Furuuchi, Keiji Browse this author | | Kawai, Yoshiko Browse this author | | Yamamoto, Yuhei Browse this author | | Sugihara, Tsuneki Browse this author | | Moriuchi, Tetsuya Browse this author |
| Keywords: | melanoma | | E-cadherin | | P-cadherin | | snail | | methylation |
| Issue Date: | Nov-2004 |
| Publisher: | Spandidos Publications |
| Journal Title: | International Journal of Oncology |
| Volume: | 25 |
| Issue: | 5 |
| Start Page: | 1415 |
| End Page: | 1421 |
| PMID: | 15492833 |
| 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/42834 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 浜田 淳一
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