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Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines

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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
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
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)

Submitter: 浜田 淳一

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