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

0361637 - BTÚ 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. E-ISSN 1083-351X
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