{"id":109214,"date":"2018-03-11T10:34:27","date_gmt":"2018-03-11T10:34:27","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/implication-of-breast-cancer-stem-cells-in-tamoxifen-resistance\/"},"modified":"2018-03-11T10:34:27","modified_gmt":"2018-03-11T10:34:27","slug":"implication-of-breast-cancer-stem-cells-in-tamoxifen-resistance","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica-molecular\/implication-of-breast-cancer-stem-cells-in-tamoxifen-resistance\/","title":{"rendered":"Implication of breast cancer stem cells in tamoxifen resistance"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Marco Piva <\/strong><\/h2>\n<p>Breast cancer is the most prevalent type of cancer in women. Tamoxifen is one of the most widely used endocrine therapy for estrogen receptor-positive, er(+), breast cancer. However, development of resistance to therapy and the consequent disease recurrence following treatment represent a serious problem. Recent findings suggest that a small cancer stem cell (csc) population is the origin of cancer and could be responsible for resistance to radio and chemotherapy leading to tumour relapse. To address the possibility that cscs play a role in the development of resistance to tamoxifen, we developed tamoxifen-resistant mcf-7 breast cancer cells (mcf- 7tamr) as a model. The proliferation rate and er expression levels of these cells were not affected, although a reduced er transcription activity was observed. Mcf- 7tamr cells showed increased stem\/progenitor cell properties, as measured by mammosphere (ms) formation assays, and proportion of csc subpopulations, and were more invasive, properties associated with tumorigenesis and poor prognosis. mcf-7tamr cells presented strong upregulation of the embryonic stem cell factor sox2. Sox2 gene silencing reduced the efficiency of ms formation, the proportion of cd44+cd24-\/low cells and aldh activity, indicating the relevance of sox2 to the stem\/progenitor cell phenotype in mcf-7tamr cells. Immunocytochemical analysis of sox2 and er revealed that while some mcf-7tamr cells coexpressed sox2 and er, there was an inverse correlation between sox2 and er expression in the stem cell population, suggesting that sox2 positive cells are more resistant to tamoxifen. consistent with this, ectopic expression of sox2 in mcf-7 cells reduced their sensitivity to the growth-inhibitory effects of tamoxifen. Taken together, these results indicate that development of resistance to tamoxifen correlates with an increase in the proportion of stem\/progenitor cells driven by the upregulation of sox2.  resumen el c\u00e1ncer de mama es el tipo de c\u00e1ncer m\u00e1s prevalente en mujeres. El tamoxifeno (tam) es un f\u00e1rmaco ampliamente utilizado como terapia endocrina en pacientes con tumores que expresan el receptor de estr\u00f3geno (er+) y, a pesar de los buenos resultados iniciales, el desarrollo de resistencia a tam representa un serio problema. estudios recientes sugieren que el origen del c\u00e1ncer reside en una peque\u00f1a poblaci\u00f3n de c\u00e9lulas madre tumorales (csc) que podr\u00eda ser la responsable de la resistencia a radioterapia y quimioterapia, dando lugar a recidivas tumorales. Con el objetivo de investigar si las cscs juegan un papel importante en el desarrollo de la resistencia a tam, generamos una l\u00ednea celular de c\u00e1ncer de mama resistente a tam (mcf7tamr). observamos que la capacidad proliferativa y los niveles de expresi\u00f3n de er no se ven afectados en estas c\u00e9lulas, mientras que la actividad transcripcional de er es menor que en la l\u00ednea celular parental. Las c\u00e9lulas mcf7tamr presentaron mayor capacidad de formaci\u00f3n de mamosferas (ms) y mayor proporci\u00f3n de subpoblaciones de cscs e invasividad, propiedades asociadas a mal pron\u00f3stico. Las c\u00e9lulas mcf7tamr presentaron mayor expresi\u00f3n de sox2. El silenciamiento del gen sox2 redujo la capacidad de formar ms, la proporci\u00f3n de c\u00e9lulas cd44+cd24-\/low y la actividad de aldh, indicando la relevancia de sox2 en el fenotipo de cmts de las c\u00e9lulas mcf-7tamr. El an\u00e1lisis inmunocitoqu\u00edmico de sox2 y er demostr\u00f3 que, a pesar de que algunas c\u00e9lulas mcf-7tamr coexpresaran estas prote\u00ednas, las cscs presentaron una relaci\u00f3n inversa entre la expresi\u00f3n de sox2 y er, sugiriendo que las c\u00e9lulas sox2 positivas son mas resistentes al tam. Consistentemente, la expresi\u00f3n ect\u00f3pica de sox2 en c\u00e9lulas mcf-7 reduce la respuesta al tam. Estos resultados indican que el desarrollo de la resistencia al tam est\u00e1 relacionada con un aumento en la proporci\u00f3n de c\u00e9lulas madre mediado por una mayor expresi\u00f3n de sox2.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Implication of breast cancer stem cells in tamoxifen resistance<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Implication of breast cancer stem cells in tamoxifen resistance <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Marco Piva <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pa\u00eds vasco\/euskal herriko unibertsitatea<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 16\/06\/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 Mar Vivanco Ruiz<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: amparo Cano garcia <\/li>\n<li>Mar\u00eda  rosa Barrio olano (vocal)<\/li>\n<li>salvatore Pece (vocal)<\/li>\n<li>Ana Aranda iriarte (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Marco Piva Breast cancer is the most prevalent type of cancer in women. Tamoxifen is one of [&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":[115,12909],"tags":[24375,7262,218564,196199,190414,218565],"class_list":["post-109214","post","type-post","status-publish","format-standard","hentry","category-bioquimica-molecular","category-pais-vasco-euskal-herriko-unibertsitatea","tag-amparo-cano-garcia","tag-ana-aranda-iriarte","tag-marco-piva","tag-maria-del-mar-vivanco-ruiz","tag-maria-rosa-barrio-olano","tag-salvatore-pece"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/109214","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=109214"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/109214\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=109214"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=109214"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=109214"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}