dc.contributor.author | HOLLVILLE, EMILIE | |
dc.date.accessioned | 2011-11-21T13:24:51Z | |
dc.date.available | 2011-11-21T13:24:51Z | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011 | en |
dc.identifier.citation | Pujals A, Renouf B, Robert A, Chelouah S, Hollville E, Wiels J, Treatment with a BH3 mimetic overcomes the resistance of latency III EBV (+) cells to p53-mediated apoptosis., Cell Death & Disease, 2, e184, 2011 | en |
dc.identifier.other | Y | |
dc.description | PUBLISHED | en |
dc.description.abstract | P53 inactivation is often observed in Burkitt's lymphoma (BL) cells due to mutations in the p53 gene or overexpression of its negative regulator, murine double minute-2 (MDM2). This event is now considered an essential part of the oncogenic process. Epstein-Barr virus (EBV) is strongly associated with BL and is a cofactor in its development. We previously showed that nutlin-3, an antagonist of MDM2, activates the p53 pathway in BL cell lines harboring wild-type p53. However, nutlin-3 strongly induced apoptosis in EBV (-) or latency I EBV (+) cells, whereas latency III EBV (+) cells were much more resistant. We show here that this resistance to apoptosis is also observed in latency III EBV (+) lymphoblastoid cell lines. We also show that, in latency III EBV (+) cells, B-cell lymphona 2 (Bcl-2) is selectively overproduced and interacts with Bcl-2-associated X protein (Bax), preventing its activation. The treatment of these cells with the Bcl-2-homology domain 3 mimetic ABT-737 disrupts Bax/Bcl-2 interaction and allows Bax activation by nutlin-3. Furthermore, treatment with these two compounds strongly induces apoptosis. Thus, a combination of Mdm2 and Bcl-2 inhibitors might be a useful anti-cancer strategy for diseases linked to EBV infection. | en |
dc.description.sponsorship | This work was supported by grants from the Fondation
de France 00012093 (JW), the Cance'ropole and Re'gion Ile-de-France (ERABL,
IF09-2092/R), the Association pour la recherche sur le Cancer 3454 (JW and EH)
and the Universite' Paris-Sud 11 (BQR 2009). We thank Yann Le'cluse for expert
technical assistance in performing ?ow cytometry analysis. | en |
dc.language.iso | en | en |
dc.publisher | Nature | en |
dc.relation.ispartofseries | Cell Death & Disease; | |
dc.relation.ispartofseries | 2; | |
dc.relation.ispartofseries | e184; | |
dc.rights | Y | en |
dc.subject | Genetics | en |
dc.subject | Oncology | en |
dc.subject | Burkitt's lymphoma | en |
dc.title | Treatment with a BH3 mimetic overcomes the resistance of latency III EBV (+) cells to p53-mediated apoptosis. | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/hollvile | |
dc.identifier.rssinternalid | 75982 | |
dc.identifier.rssuri | http://dx.doi.org/10.1038/cddis.2011.67 | |
dc.identifier.uri | http://hdl.handle.net/2262/60880 | |