| RRC ID |
6495
|
| 著者 |
Tsutsumida A, Hamada J, Tada M, Aoyama T, Furuuchi K, Kawai Y, Yamamoto Y, Sugihara T, Moriuchi T.
|
| タイトル |
Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines.
|
| ジャーナル |
Int J Oncol
|
| 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.
|
| 巻・号 |
25(5)
|
| ページ |
1415-21
|
| 公開日 |
2004-11-1
|
| PMID |
15492833
|
| MeSH |
Cadherins / biosynthesis*
DNA Methylation
DNA-Binding Proteins / pharmacology
Down-Regulation
Gene Expression Profiling*
Gene Silencing*
Humans
Melanoma / genetics*
Melanoma / pathology*
Promoter Regions, Genetic
Skin Neoplasms / genetics*
Skin Neoplasms / pathology*
Snail Family Transcription Factors
Transcription Factors / pharmacology
Tumor Cells, Cultured
Zinc Fingers
|
| IF |
3.899
|
| 引用数 |
25
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
AKI(RCB0408)
MMAc(RCB0808) |
