{"id":107425,"date":"2018-03-11T10:31:45","date_gmt":"2018-03-11T10:31:45","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/regulacion-de-la-expresion-de-la-isoforma-oncogenica-deltaex2p73-por-la-anfirregulina-ar-un-nuevo-mecanismo-en-el-proceso-de-hepatocarcinogenesis\/"},"modified":"2018-03-11T10:31:45","modified_gmt":"2018-03-11T10:31:45","slug":"regulacion-de-la-expresion-de-la-isoforma-oncogenica-deltaex2p73-por-la-anfirregulina-ar-un-nuevo-mecanismo-en-el-proceso-de-hepatocarcinogenesis","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/navarra\/regulacion-de-la-expresion-de-la-isoforma-oncogenica-deltaex2p73-por-la-anfirregulina-ar-un-nuevo-mecanismo-en-el-proceso-de-hepatocarcinogenesis\/","title":{"rendered":"Regulaci\u00f3n de la expresi\u00f3n de la isoforma oncog\u00e9nica deltaex2p73 por la anfirregulina (ar): un nuevo mecanismo en el proceso de hepatocarcinog\u00e9nesis"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Saioa Go\u00f1i Irigoyen <\/strong><\/h2>\n<p>La anfirregulina (ar) es un factor de crecimiento de la familia del factor de crecimiento epid\u00c2\u00bf\u00c2\u00bfrmico (egf) que no se expresa en el h\u00c2\u00bf\u00aagado sano. Sin embargo nuestros datos previos muestran que su expresi\u00c2\u00bf\u00c2\u00aen se ve inducida en muestras de pacientes con cirrosis y con hepatocarcinoma (hcc), siendo un factor esencial para la supervivencia de las c\u00c2\u00bf\u00c2\u00bflulas de hcc. Por su parte p73 es un gen supresor de tumores de la familia de p53, que a trav\u00c2\u00bf\u00c2\u00bfs de un mecanismo de splicing alternativo de su extremo amino-terminal, da lugar a diferentes isoformas dominantes negativas tanto de p73 como de p53. Nuestros datos confirman que la isoforma oncog\u00c2\u00bf\u00c2\u00bfnica \u00c2\u00bf\u00c2\u00bfex2p73 se induce en muestras de hcc, y demuestran por primera vez su inducci\u00c2\u00bf\u00c2\u00aen en muestras preneopl\u00c2\u00bf\u00c2\u00a2sicas como la cirrosis y en muestras de h\u00c2\u00bf\u00aagados sanos que albergan un hcc o una met\u00c2\u00bf\u00c2\u00a2stasis de colon. En todas las muestras analizadas la expresi\u00c2\u00bf\u00c2\u00aen de \u00c2\u00bf\u00c2\u00bfex2p73 se correlaciona de forma directa y significativa con la expresi\u00c2\u00bf\u00c2\u00aen de la ar. La inducci\u00c2\u00bf\u00c2\u00aen de la isoforma oncog\u00c2\u00bf\u00c2\u00bfnica \u00c2\u00bf\u00c2\u00bfex2p73 en muestras de h\u00c2\u00bf\u00aagado humano es funcional y se correlaciona de forma inversa con la expresi\u00c2\u00bf\u00c2\u00aen de genes diana de p73, como por ejemplo, el factor derivado del epitelio pigmentado (pedf) importante inhibidor de la angiog\u00c2\u00bf\u00c2\u00bfnesis. Nuestros datos muestran que la ar a trav\u00c2\u00bf\u00c2\u00bfs del egfr y de manera dependiente de la kinasa jnk1, activa al factor de transcripci\u00c2\u00bf\u00c2\u00aen elk-1 promoviendo su asociaci\u00c2\u00bf\u00c2\u00aen con el promotor de slu7 e inhibiendo su expresi\u00c2\u00bf\u00c2\u00aen. La disminuci\u00c2\u00bf\u00c2\u00aen de la expresi\u00c2\u00bf\u00c2\u00aen del factor de splicing slu7 favorece la exclusi\u00c2\u00bf\u00c2\u00aen del ex\u00c2\u00bf\u00c2\u00aen 2 de p73, gener\u00c2\u00bf\u00c2\u00a2ndose la isoforma oncog\u00c2\u00bf\u00c2\u00bfnica \u00c2\u00bf\u00c2\u00bfex2p73 e inhibi\u00c2\u00bf\u00c2\u00bfndose la expresi\u00c2\u00bf\u00c2\u00aen de los genes diana de p73. De forma llamativa, la ar es capaz de activar esta v\u00c2\u00bf\u00aaa en hepatocitos normales, sugiriendo que la inducci\u00c2\u00bf\u00c2\u00aen de la relaci\u00c2\u00bf\u00c2\u00aen \u00c2\u00bf\u00c2\u00bfex2p73\/tap73 por la ar puede ser un evento temprano en la hepatocarcinog\u00c2\u00bf\u00c2\u00bfnesis.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Regulaci\u00f3n de la expresi\u00f3n de la isoforma oncog\u00e9nica deltaex2p73 por la anfirregulina (ar): un nuevo mecanismo en el proceso de hepatocarcinog\u00e9nesis<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Regulaci\u00f3n de la expresi\u00f3n de la isoforma oncog\u00e9nica deltaex2p73 por la anfirregulina (ar): un nuevo mecanismo en el proceso de hepatocarcinog\u00e9nesis <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Saioa Go\u00f1i Irigoyen <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 18\/03\/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>Mar\u00eda  Del Carmen Berasain Lasarte<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jes\u00fas m. Prieto valtue\u00f1a <\/li>\n<li>Elena Ruiz Garc\u00eda-trevijano (vocal)<\/li>\n<li>aranzazu S\u00e1nchez mu\u00f1oz (vocal)<\/li>\n<li>Luis Alvarez garcia (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Saioa Go\u00f1i Irigoyen La anfirregulina (ar) es un factor de crecimiento de la familia del factor de [&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":[36483,17749],"tags":[93311,156298,15059,44788,80799,215779],"class_list":["post-107425","post","type-post","status-publish","format-standard","hentry","category-biologia-molecular","category-navarra","tag-aranzazu-sanchez-munoz","tag-elena-ruiz-garcia-trevijano","tag-jesus-m-prieto-valtuena","tag-luis-alvarez-garcia","tag-maria-del-carmen-berasain-lasarte","tag-saioa-goni-irigoyen"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/107425","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=107425"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/107425\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=107425"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=107425"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=107425"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}