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Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism
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SYSNO ASEP 0361637 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism Tvůrce(i) Nocchi, L. (IT)
Tomasetti, M. (IT)
Amati, M. (IT)
Neužil, Jiří (BTO-N) RID
Santarelli, L. (IT)
Saccucci, F. (IT)Zdroj.dok. Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 286, č. 22 (2011), s. 19478-19488Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova Thrombomodulin gene promoter ; malignant mesothelioma ; poly(ADP-ribose) polymerase-1 Vědní obor RIV EB - Genetika a molekulární biologie CEP GA204/08/0811 GA ČR - Grantová agentura ČR CEZ AV0Z50520701 - BTO-N (2007-2013) UT WOS 000291027700031 DOI 10.1074/jbc.M110.217331 Anotace 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. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2012
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