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

  • Authors:
    • Arata Tsutsumida
    • Jun-ichi Hamada
    • Mitsuhiro Tada
    • Tetsuya Aoyama
    • Keiji Furuuchi
    • Yoshiko Kawai
    • Yuhei Yamamoto
    • Tsuneki Sugihara
    • Tetsuya Moriuchi
  • View Affiliations

  • Published online on: November 1, 2004     https://doi.org/10.3892/ijo.25.5.1415
  • Pages: 1415-1421
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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.

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November 2004
Volume 25 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Tsutsumida A, Hamada J, Tada M, Aoyama T, Furuuchi K, Kawai Y, Yamamoto Y, Sugihara T and Moriuchi T: Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines. Int J Oncol 25: 1415-1421, 2004
APA
Tsutsumida, A., Hamada, J., Tada, M., Aoyama, T., Furuuchi, K., Kawai, Y. ... Moriuchi, T. (2004). Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines. International Journal of Oncology, 25, 1415-1421. https://doi.org/10.3892/ijo.25.5.1415
MLA
Tsutsumida, A., Hamada, J., Tada, M., Aoyama, T., Furuuchi, K., Kawai, Y., Yamamoto, Y., Sugihara, T., Moriuchi, T."Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines". International Journal of Oncology 25.5 (2004): 1415-1421.
Chicago
Tsutsumida, A., Hamada, J., Tada, M., Aoyama, T., Furuuchi, K., Kawai, Y., Yamamoto, Y., Sugihara, T., Moriuchi, T."Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines". International Journal of Oncology 25, no. 5 (2004): 1415-1421. https://doi.org/10.3892/ijo.25.5.1415