Involvement of Ets-1 transcription factor in inducing matrix metalloproteinase-2 expression by epithelial-mesenchymal transition in human squamous carcinoma cells

  • Authors: Masayuki Taki, Kristin Verschueren, Kazuhiro Yokoyama, Masaru Nagayama, Nobuyuki Kamata
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  • Published online on: Wednesday, February 1, 2006
  • Pages: 487-496
  • DOI: 10.3892/ijo.28.2.487

Abstract

Epithelial-mesenchymal transition (EMT) is a crucial event in cancer progression. We previously reported that EMT up-regulates matrix metalloproteinase-2 (MMP-2) expression in squamous cell carcinoma (SCC) cells. In this study, we showed that Tet Off-induced expression of Snail or SIP1, and treatment with TGF-β1 induced EMT in terms of down-regulation of E-cadherin, and up-regulation of vimentin and MMP-2 expression with morphological changes. In SCC cells, SIP1 expression was induced by Snail and TGF-β1, but Snail expression was not induced by SIP1 or TGF-β1. However, expression of Snail but not SIP1 was strongly increased by TGF-β1 in highly invasive SCC cells with mesenchymal phenotypes. Analysis of the MMP-2 promoter revealed that an Ets-1 binding site, located between position -1255 and -1248 relative to the transcriptional start site, was critical for the activation by Snail, SIP1 and TGF-β1 in SCC cells. Induced expression of Snail and SIP1 resulted in the increased expression of Ets-1 and DNA-binding activities of nuclear proteins to the Ets-1-binding site and strong Ets-1 expression was detected in highly invasive SCC cells. Furthermore, overexpression of Ets-1 induced the promoter-activation and expression of MMP-2 without EMT. These results indicate that EMT induces Ets-1 expression, which activates the MMP-2 promoter, but Ets-1 by itself has no activity to induce EMT in SCC cells.
Journal Cover

February 2006
Volume 28 Issue 2

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

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Taki, M., Verschueren, K., Yokoyama, K., Nagayama, M., & Kamata, N. (2006). Involvement of Ets-1 transcription factor in inducing matrix metalloproteinase-2 expression by epithelial-mesenchymal transition in human squamous carcinoma cells. International Journal of Oncology, 28(2), 487-496.
MLA
Taki, Verschueren, Yokoyama, Nagayama, and Nobuyuki Kamata. "Involvement of Ets-1 transcription factor in inducing matrix metalloproteinase-2 expression by epithelial-mesenchymal transition in human squamous carcinoma cells." International Journal of Oncology International Journal of Oncology 28.2 (2006): 487-496.
Chicago
Taki, Verschueren, Yokoyama, Nagayama, and Nobuyuki Kamata. "Involvement of Ets-1 transcription factor in inducing matrix metalloproteinase-2 expression by epithelial-mesenchymal transition in human squamous carcinoma cells." International Journal of Oncology International Journal of Oncology 28 no. 2 (2006): 487-496.