Epigenetic regulation of proMMP-1 expression in the HT1080 human fibrosarcoma cell line

  • Authors:
    • Mathilde Poplineau
    • Jean Dufer
    • Frank Antonicelli
    • Aurelie Trussardi-Regnier
  • View Affiliations

  • Published online on: March 17, 2011     https://doi.org/10.3892/ijo.2011.975
  • Pages: 1713-1718
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Abstract

The matrix metalloproteinase (MMP) family members play an important role in various physiological and pathological processes. Although MMP-1 (collagenase-1) has been shown to be involved in tumor invasiveness, the regulation of its expression is still not fully elucidated and could implicate epigenetic mechanisms. The aim of this study was to analyze the effects of the Histone Deacetylase Inhibitor (HDI) trichostatin A (TSA) and the inhibitor of DNA methylation 5-aza-2'-deoxycytidine (5-azadC) on the proMMP-1 expression in the human HT1080 fibrosarcoma cell line. Real-time RT-PCR revealed that 5-azadC or 5-azadC + TSA but not TSA alone, despite global histone H4 hyperacetylation, increased proMMP-1 mRNA levels. This transcription activation was correlated with chromatin decondensation determined by nuclear texture image analysis technique. Western blot analysis of cell culture conditioned media revealed a significant increase in proMMP-1 secretion after 5-azadC or 5-azadC + TSA treatment compared to untreated cells. These results suggested that epigenetic mechanisms could be involved in proMMP-1 gene expression including chromatin supra-organization changes. Indeed, although the proMMP-1 gene promoter does not appear to contain CpG islands, its expression can be induced by the demethylating agent 5-azadC. Further experiments revealed that inhibition of protein neosynthesis by cycloheximide decreased 5-azadC-induced proMMP-1 mRNA, suggesting that epigenetically regulated intermediate molecules could be involved in proMMP-1 expression regulation in these cells.

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June 2011
Volume 38 Issue 6

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

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Spandidos Publications style
Poplineau M, Dufer J, Antonicelli F and Trussardi-Regnier A: Epigenetic regulation of proMMP-1 expression in the HT1080 human fibrosarcoma cell line. Int J Oncol 38: 1713-1718, 2011.
APA
Poplineau, M., Dufer, J., Antonicelli, F., & Trussardi-Regnier, A. (2011). Epigenetic regulation of proMMP-1 expression in the HT1080 human fibrosarcoma cell line. International Journal of Oncology, 38, 1713-1718. https://doi.org/10.3892/ijo.2011.975
MLA
Poplineau, M., Dufer, J., Antonicelli, F., Trussardi-Regnier, A."Epigenetic regulation of proMMP-1 expression in the HT1080 human fibrosarcoma cell line". International Journal of Oncology 38.6 (2011): 1713-1718.
Chicago
Poplineau, M., Dufer, J., Antonicelli, F., Trussardi-Regnier, A."Epigenetic regulation of proMMP-1 expression in the HT1080 human fibrosarcoma cell line". International Journal of Oncology 38, no. 6 (2011): 1713-1718. https://doi.org/10.3892/ijo.2011.975