Počet záznamů: 1

Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism

  1. 1.
    0361637 - BTO-N 2012 RIV US eng J - Článek v odborném periodiku
    Nocchi, L. - Tomasetti, M. - Amati, M. - Neužil, Jiří - Santarelli, L. - Saccucci, F.
    Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism.
    Journal of Biological Chemistry. Roč. 286, č. 22 (2011), s. 19478-19488 ISSN 0021-9258
    Grant CEP: GA ČR(CZ) GA204/08/0811
    Výzkumný záměr: CEZ:AV0Z50520701
    Klíčová slova: Thrombomodulin gene promoter * malignant mesothelioma * poly(ADP-ribose) polymerase-1
    Kód oboru RIV: EB - Genetika a molekulární biologie
    Impakt faktor: 4.773, rok: 2011

    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.
    Trvalý link: http://hdl.handle.net/11104/0198906