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A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma

dc.contributor.authorBeltran, Elena
dc.contributor.authorFresquet, Vicente
dc.contributor.authorMartinez-Useros, Javier
dc.contributor.authorRichter-Larrea, Jose A.
dc.contributor.authorSagardoy, Ainara
dc.contributor.authorSesma, Izaskun
dc.contributor.authorAlmada, Luciana L.
dc.contributor.authorMontes-Serrano, Santiago
dc.contributor.authorSiebert, Reiner
dc.contributor.authorGesk, Stefan
dc.contributor.authorCalasanz, María J.
dc.contributor.authorMalumbres, Raquel
dc.contributor.authorRieger, Melissa
dc.contributor.authorProsper, Felipe
dc.contributor.authorLossos, Izidore S.
dc.contributor.authorPiris, Miguel Angel
dc.contributor.authorFernandez-Zapico, Martin E.
dc.contributor.authorMartinez-Climent, Jose A.
dc.identifier.citationE. Beltran, V. Fresquet, J. Martinez-Useros, et al. A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma. Proc Natl Acad Sci USA, 108 (2011), pp. 12461-12466es
dc.descriptionArtículo publicado en 2011. La revista está indexada en: Science Citation Index Expanded (Clarivate), Scopus (ELSEVIER), DIALNET (Universidad de la Rioja), Agricultural & Environmental Science Database (ProQuest), Animal Behavior Abstracts (ProQuest), Aquatic Science & Fisheries Abstracts - ASFA (Food and Agriculture Organization - FAO) [ProQuest], Artic & Antarctic Regions (EBSCO), BIOSIS (Clarivate), CAB Abstracts (CABI), Chemical Abstracts Core (American Chemical Society), EMBASE (ELSEVIER), Food Science & Technology Abstracts (International Food Information Service), INSPEC (The Institution of Engineering and Technology), Linguistic Bibliography (Brill), MEDLINE (United States National Library of Medicine), Pollution Abstracts (ProQuest), Public Affairs Index (EBSCO), RILM Abstracts of Music Literature (Répertoire International de Littérature Musicale), Veterinary Science Database (CABI), EconLit (American Economic Association), MathSciNet (American Mathematical Society), Psycinfo (American Psychological Association - APA), zbMATH Proceedings of the National Academy of Sciences of the United States of America, es la publicación oficial de la Academia Nacional de Ciencias de Estados Unidos. Publicada por primera vez en 1915, aunque la revista cubre las ciencias sociales, biológicas y físicas, su mayor enfoque está en las ciencias biomédicas. ISSN: 0027-8424, EISSN: 1091-6490 En el año 2011 esta revista tuvo un total de 504.243 citas -JCR: Tiene la clasificación de MULTIDISCIPLINARY SCIENCES donde se sitúa en la posición 3 de 56 revistas en el año 2011. Con un índice de impacto JCR (2011) de 9.681; y un índice de impacto a 5 años de 10.472. Con un JIF percentil de 95.54 pertenece al D1. Eigenfactor Score: 1.60168. -SCOPUS: Tiene la clasificación de MULTIDISCIPLINARY donde se sitúa en la posición 3 de 94 revistas en el año 2011. Situada en un percentil 97que pertenece al D1. -Número de citas a 22/12/2023 según PNAS ha sido de 39 y de visualizaciones: 4532. El número de citas según SCOPUS es de 44. Según Google Schoolar: 64 y según Web of science: 45. -CiteScore en 2011 es de 16.8 -Esta publicación es Open Accesses
dc.description.abstractThe chromosomal translocationt(11;14)(q13;q32) leading to cyclin-D1 overexpression plays an essential role in the development ofmantle cell lymphoma (MCL), an aggressive tumor that remains in-curable with current treatment strategies. Cyclin-D1 has been pos-tulated as an effective therapeutic target, but the evaluation of thistarget has been hampered by our incomplete understanding of itsoncogenic functions and by the lack of valid MCL murine models. Toaddress these issues, we generated a cyclin-D1–driven mouse modelin which cyclin-D1 expression can be regulated externally. Thesemice developed cyclin-D1–expressing lymphomas capable of recapit-ulating features of human MCL. We found that cyclin-D1 inactiva-tion was not sufficient to induce lymphoma regression in vivo;however, using a combination of in vitro and in vivo assays, weidentified a novel prosurvival cyclin-D1 function in MCL cells. Specif-ically, we found that cyclin-D1, besides increasing cell proliferationthrough deregulation of the cell cycle at the G1–S transition, seques-trates the proapoptotic protein BAX in the cytoplasm, thereby fa-voring BCL2’s antiapoptotic function. Accordingly, cyclin-D1 inhi-bition sensitized the lymphoma cells to apoptosis through BAXrelease. Thus, genetic or pharmacologic targeting of cyclin-D1 com-bined with a proapoptotic BH3 mimetic synergistically killed thecyclin-D1–expressing murine lymphomas, human MCL cell lines,and primary lymphoma cells. Our study identifies a role of cyclin-D1 in deregulating apoptosis in MCL cells, and highlights the poten-tial benefit of simultaneously targeting cyclin-D1 and survival path-ways in patients with MCL. This effective combination therapy alsomight be exploited in other cyclin-D1–expressing
dc.publisherNational Academy of Sciences of the United States of Americaes
dc.subjectmouse model of MCLes
dc.subjectcyclin-D1 inhibitor drugses
dc.subjecttargeted therapyes
dc.subjectoncogene addictiones
dc.titleA cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphomaes

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