{"id":112122,"date":"2018-03-11T10:39:00","date_gmt":"2018-03-11T10:39:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/generacion-y-caracterizacion-de-modelos-de-linfoma-de-celulas-del-manto-con-expresion-regulable-de-ciclina-d1-y-sobre-expresion-de-bc12-o-c-myc\/"},"modified":"2018-03-11T10:39:00","modified_gmt":"2018-03-11T10:39:00","slug":"generacion-y-caracterizacion-de-modelos-de-linfoma-de-celulas-del-manto-con-expresion-regulable-de-ciclina-d1-y-sobre-expresion-de-bc12-o-c-myc","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/hemopatologia\/generacion-y-caracterizacion-de-modelos-de-linfoma-de-celulas-del-manto-con-expresion-regulable-de-ciclina-d1-y-sobre-expresion-de-bc12-o-c-myc\/","title":{"rendered":"Generaci\u00f3n y caracterizaci\u00f3n de modelos de linfoma de c\u00e9lulas del manto con expresi\u00f3n regulable de ciclina d1 y sobre-expresi\u00f3n de bc12 o c-myc"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Javier Martinez Useros <\/strong><\/h2>\n<p>The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-d1 overexpression plays an essential role in the development of mantle cell lymphoma (mcl), an aggressive tumor that remains incurable with current treatment strategies. Cyclin-d1 has been postulated as an effective therapeutic target, but the evaluation of this target has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid mcl murine models. To address these issues, we generated a cyclin-d1\u00c2\u00bfdriven mouse model in which cyclin-d1 expression can be regulated externally. In addition, this cyclin-d1-driven mouse model has been complemented with bcl2 or c-myc overexpression. These mice are capable of recapitulating features of human mcl. We found that cyclin-d1 inactivation was not sufficient to induce lymphoma regression in vivo; however, using a combination of in vitro and in vivo assays, we identified a novel prosurvival cyclin-d1 function in mcl cells. Specifically, we found that cyclin-d1, besides increasing cell proliferation through deregulation of the cell cycle at the g1\u00c2\u00bfs transition, sequestrates the proapoptotic protein bax in the cytoplasm, thereby favoring bcl2\u00c2\u00bfs antiapoptotic function. Accordingly, cyclin-d1 inhibition sensitized the lymphoma cells to apoptosis through bax release. Thus, genetic or pharmacologic targeting of cyclin-d1 combined with a proapoptotic bh3 mimetic synergistically killed the cyclin-d1\u00c2\u00bfexpressing murine lymphomas cells. Our study identifies a role of cyclin-d1 in deregulating apoptosis in mcl cells, and highlights the potential benefit of simultaneously targeting cyclin-d1 and survival pathways in patients with mcl.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Generaci\u00f3n y caracterizaci\u00f3n de modelos de linfoma de c\u00e9lulas del manto con expresi\u00f3n regulable de ciclina d1 y sobre-expresi\u00f3n de bc12 o c-myc<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Generaci\u00f3n y caracterizaci\u00f3n de modelos de linfoma de c\u00e9lulas del manto con expresi\u00f3n regulable de ciclina d1 y sobre-expresi\u00f3n de bc12 o c-myc <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Javier Martinez Useros <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 20\/12\/2011<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Jos\u00e9 \u00e1ngel Mart\u00ednez Climent<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: africa Garcia orad <\/li>\n<li>dolors Colomer pujol (vocal)<\/li>\n<li>Mar\u00eda  de la cruz Viguria alegria (vocal)<\/li>\n<li>paloma Virseda chamorro (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Javier Martinez Useros The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-d1 overexpression plays an essential role in the [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[849,36483,195,17749,1027],"tags":[200330,118385,223197,120167,158472,32553],"class_list":["post-112122","post","type-post","status-publish","format-standard","hentry","category-biologia-celular","category-biologia-molecular","category-hemopatologia","category-navarra","category-oncologia","tag-africa-garcia-orad","tag-dolors-colomer-pujol","tag-javier-Martinez-useros","tag-jose-angel-Martinez-climent","tag-maria-de-la-cruz-viguria-alegria","tag-paloma-virseda-chamorro"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/112122","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=112122"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/112122\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=112122"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=112122"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=112122"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}