Cargando…

Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer

Tamoxifen(TAM) is one of the most effective endocrine treatment for estrogen receptor(ER)-positive breast cancer, however drug resistance greatly limits benefit of it. Our purpose is to uncover the role of Beclin 1 in tamoxifen resistance and prognosis of ER positive breast cancer. We established a...

Descripción completa

Detalles Bibliográficos
Autores principales: Gu, Yu, Chen, Tianxiang, Li, Guangliang, Xu, Cong, Xu, Zhenzhen, Zhang, Jing, He, Kuifeng, Zheng, Linyan, Guan, Zhonghai, Su, Xinyun, Cao, Jiang, Teng, Lisong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581020/
https://www.ncbi.nlm.nih.gov/pubmed/28881721
http://dx.doi.org/10.18632/oncotarget.11044
_version_ 1783260980129562624
author Gu, Yu
Chen, Tianxiang
Li, Guangliang
Xu, Cong
Xu, Zhenzhen
Zhang, Jing
He, Kuifeng
Zheng, Linyan
Guan, Zhonghai
Su, Xinyun
Cao, Jiang
Teng, Lisong
author_facet Gu, Yu
Chen, Tianxiang
Li, Guangliang
Xu, Cong
Xu, Zhenzhen
Zhang, Jing
He, Kuifeng
Zheng, Linyan
Guan, Zhonghai
Su, Xinyun
Cao, Jiang
Teng, Lisong
author_sort Gu, Yu
collection PubMed
description Tamoxifen(TAM) is one of the most effective endocrine treatment for estrogen receptor(ER)-positive breast cancer, however drug resistance greatly limits benefit of it. Our purpose is to uncover the role of Beclin 1 in tamoxifen resistance and prognosis of ER positive breast cancer. We established a tamoxifen resistant ER-positive breast cancer cell subline MCF-7R presenting with higher Beclin 1 and human epidermal growth factor receptor 2(HER2) levels than MCF-7. Silencing Beclin 1 decreased levels of HER2 and significantly promoted TAM sensitivity of MCF-7 and MCF-7R in vitro. Overexpression of HER2 could reverse TAM sensitivity, which was formerly increased in Beclin 1 downregulated cell. Beclin 1 level was not only positively correlated with level of HER2 but also negatively correlated with overall survival of ER-positive breast cancer patients. Using bioinformatic methods, Beclin 1 mRNA was found to be negatively correlated with overall survival in breast cancer patients receiving TAM treatment. This study indicated for the first time that lower HER2 expression by Beclin 1 downregulation contributes to alteration of tamoxifen sensitivity and low Beclin 1 predicts favorable outcome in ER-positive breast cancer.
format Online
Article
Text
id pubmed-5581020
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-55810202017-09-06 Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer Gu, Yu Chen, Tianxiang Li, Guangliang Xu, Cong Xu, Zhenzhen Zhang, Jing He, Kuifeng Zheng, Linyan Guan, Zhonghai Su, Xinyun Cao, Jiang Teng, Lisong Oncotarget Research Paper Tamoxifen(TAM) is one of the most effective endocrine treatment for estrogen receptor(ER)-positive breast cancer, however drug resistance greatly limits benefit of it. Our purpose is to uncover the role of Beclin 1 in tamoxifen resistance and prognosis of ER positive breast cancer. We established a tamoxifen resistant ER-positive breast cancer cell subline MCF-7R presenting with higher Beclin 1 and human epidermal growth factor receptor 2(HER2) levels than MCF-7. Silencing Beclin 1 decreased levels of HER2 and significantly promoted TAM sensitivity of MCF-7 and MCF-7R in vitro. Overexpression of HER2 could reverse TAM sensitivity, which was formerly increased in Beclin 1 downregulated cell. Beclin 1 level was not only positively correlated with level of HER2 but also negatively correlated with overall survival of ER-positive breast cancer patients. Using bioinformatic methods, Beclin 1 mRNA was found to be negatively correlated with overall survival in breast cancer patients receiving TAM treatment. This study indicated for the first time that lower HER2 expression by Beclin 1 downregulation contributes to alteration of tamoxifen sensitivity and low Beclin 1 predicts favorable outcome in ER-positive breast cancer. Impact Journals LLC 2016-08-04 /pmc/articles/PMC5581020/ /pubmed/28881721 http://dx.doi.org/10.18632/oncotarget.11044 Text en Copyright: © 2017 Gu et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Gu, Yu
Chen, Tianxiang
Li, Guangliang
Xu, Cong
Xu, Zhenzhen
Zhang, Jing
He, Kuifeng
Zheng, Linyan
Guan, Zhonghai
Su, Xinyun
Cao, Jiang
Teng, Lisong
Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer
title Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer
title_full Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer
title_fullStr Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer
title_full_unstemmed Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer
title_short Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer
title_sort lower beclin 1 downregulates her2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for er positive breast cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581020/
https://www.ncbi.nlm.nih.gov/pubmed/28881721
http://dx.doi.org/10.18632/oncotarget.11044
work_keys_str_mv AT guyu lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT chentianxiang lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT liguangliang lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT xucong lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT xuzhenzhen lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT zhangjing lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT hekuifeng lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT zhenglinyan lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT guanzhonghai lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT suxinyun lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT caojiang lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer
AT tenglisong lowerbeclin1downregulatesher2expressiontoenhancetamoxifensensitivityandpredictsafavorableoutcomeforerpositivebreastcancer