About: Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism     Goto   Sponge   NotDistinct   Permalink

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  • We analyzed thrombomodulin (TM) expression in biopsies of malignant mesothelioma (MM) patients and compared with normal mesothelial tissue. To evaluate poly(ADP-ribose) polymerase-1 (PARP1) as responsible for gene promoter epigenetic modifications, nonmalignant mesothelial cells (Met-5A) and MM cells (H28) were silenced for PARP1 and the DNA methylation/acetylation-associated TM expression evaluated. A correlation between low TM expression and high level of TM promoter methylation was found in MM biopsies. Low expression of TM was restored in MM cells by treatment with 5-aza-2'-deoxycytidine and trichostatin, whereas the epigenetic agents did not affect TM expression in Met-5A cells. Silencing of PARP1 resulted in a strong down-regulation of TM expression in Met-5A cells, while restoring TM expression in H28 cells. PARP1 silencing induced TM promoter methylation in Met-5A cells and demethylation in MM cells, and this was paralleled by changes in the DNA methyltransferase activity.
  • We analyzed thrombomodulin (TM) expression in biopsies of malignant mesothelioma (MM) patients and compared with normal mesothelial tissue. To evaluate poly(ADP-ribose) polymerase-1 (PARP1) as responsible for gene promoter epigenetic modifications, nonmalignant mesothelial cells (Met-5A) and MM cells (H28) were silenced for PARP1 and the DNA methylation/acetylation-associated TM expression evaluated. A correlation between low TM expression and high level of TM promoter methylation was found in MM biopsies. Low expression of TM was restored in MM cells by treatment with 5-aza-2'-deoxycytidine and trichostatin, whereas the epigenetic agents did not affect TM expression in Met-5A cells. Silencing of PARP1 resulted in a strong down-regulation of TM expression in Met-5A cells, while restoring TM expression in H28 cells. PARP1 silencing induced TM promoter methylation in Met-5A cells and demethylation in MM cells, and this was paralleled by changes in the DNA methyltransferase activity. (en)
Title
  • Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism
  • Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism (en)
skos:prefLabel
  • Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism
  • Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism (en)
skos:notation
  • RIV/86652036:_____/11:00361637!RIV12-AV0-86652036
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(GA204/08/0811), Z(AV0Z50520701)
http://linked.open...iv/cisloPeriodika
  • 22
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  • 235308
http://linked.open...ai/riv/idVysledku
  • RIV/86652036:_____/11:00361637
http://linked.open...riv/jazykVysledku
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  • Thrombomodulin gene promoter; malignant mesothelioma; poly(ADP-ribose) polymerase-1 (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [96B3D19CE9F4]
http://linked.open...i/riv/nazevZdroje
  • Journal of Biological Chemistry
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http://linked.open...ichTvurcuVysledku
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http://linked.open...vavai/riv/projekt
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  • 286
http://linked.open...iv/tvurceVysledku
  • Amati, M.
  • Neužil, Jiří
  • Nocchi, L.
  • Saccucci, F.
  • Santarelli, L.
  • Tomasetti, M.
http://linked.open...ain/vavai/riv/wos
  • 000291027700031
http://linked.open...n/vavai/riv/zamer
issn
  • 0021-9258
number of pages
http://bibframe.org/vocab/doi
  • 10.1074/jbc.M110.217331
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