Cargando…

Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells

BACKGROUNDS: Tamoxifen is typically used to treat patients with estrogen receptor alpha (ERα)-positive breast cancer. However, 30% of these patients gain acquired resistance to tamoxifen during or after tamoxifen treatment. As a Ras modulator, Nogo-B receptor (NgBR) is required for tumorigenesis thr...

Descripción completa

Detalles Bibliográficos
Autores principales: Gao, Pin, Wang, Xiang, Jin, Ying, Hu, Wenquan, Duan, Yajun, Shi, Aiping, Du, Ye, Song, Dong, Yang, Ming, Li, Sijie, Han, Bing, Zhao, Gang, Zhang, Hongquan, Fan, Zhimin, Miao, Qing Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134690/
https://www.ncbi.nlm.nih.gov/pubmed/30208932
http://dx.doi.org/10.1186/s13058-018-1028-5
_version_ 1783354706092883968
author Gao, Pin
Wang, Xiang
Jin, Ying
Hu, Wenquan
Duan, Yajun
Shi, Aiping
Du, Ye
Song, Dong
Yang, Ming
Li, Sijie
Han, Bing
Zhao, Gang
Zhang, Hongquan
Fan, Zhimin
Miao, Qing Robert
author_facet Gao, Pin
Wang, Xiang
Jin, Ying
Hu, Wenquan
Duan, Yajun
Shi, Aiping
Du, Ye
Song, Dong
Yang, Ming
Li, Sijie
Han, Bing
Zhao, Gang
Zhang, Hongquan
Fan, Zhimin
Miao, Qing Robert
author_sort Gao, Pin
collection PubMed
description BACKGROUNDS: Tamoxifen is typically used to treat patients with estrogen receptor alpha (ERα)-positive breast cancer. However, 30% of these patients gain acquired resistance to tamoxifen during or after tamoxifen treatment. As a Ras modulator, Nogo-B receptor (NgBR) is required for tumorigenesis through the signaling crosstalk with epidermal growth factor (EGF) receptor (EGFR)-mediated pathways. NgBR is highly expressed in many types of cancer cells and regulates the sensitivity of hepatocellular carcinoma to chemotherapy. In this study, we found the expression of NgBR is increased in tamoxifen-resistant ERα-positive breast cancer cells. METHODS: Tamoxifen-resistant ERα-positive MCF-7 and T47D breast cancer cell lines were established by culturing with gradually increased concentration of 4-hydroxytamoxifen (4-OHT). The effects of NgBR on tamoxifen resistance was determined by depleting NgBR in these cell lines using previously validated small interfering RNA (siRNA). The effects of 4-OHT on cell viability and apoptosis were determined using well-accepted methods such as clonogenic survival assay and Annexin V/propidium iodide staining. The alteration of EGF-stimulated signaling and gene expression was determined by western blot analysis and real-time PCR, respectively. RESULTS: NgBR knockdown with siRNA attenuates EGF-induced phosphorylation of ERα and restores the sensitivity to tamoxifen in ERα-positive breast cancer cells. Mechanistically, our data demonstrated that NgBR knockdown increases the protein levels of p53 and decreases survivin, which is an apoptosis inhibitor. CONCLUSIONS: These results suggested that NgBR is a potential therapeutic target for increasing the sensitivity of ERα-positive breast cancer to tamoxifen. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-018-1028-5) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6134690
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-61346902018-09-13 Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells Gao, Pin Wang, Xiang Jin, Ying Hu, Wenquan Duan, Yajun Shi, Aiping Du, Ye Song, Dong Yang, Ming Li, Sijie Han, Bing Zhao, Gang Zhang, Hongquan Fan, Zhimin Miao, Qing Robert Breast Cancer Res Research Article BACKGROUNDS: Tamoxifen is typically used to treat patients with estrogen receptor alpha (ERα)-positive breast cancer. However, 30% of these patients gain acquired resistance to tamoxifen during or after tamoxifen treatment. As a Ras modulator, Nogo-B receptor (NgBR) is required for tumorigenesis through the signaling crosstalk with epidermal growth factor (EGF) receptor (EGFR)-mediated pathways. NgBR is highly expressed in many types of cancer cells and regulates the sensitivity of hepatocellular carcinoma to chemotherapy. In this study, we found the expression of NgBR is increased in tamoxifen-resistant ERα-positive breast cancer cells. METHODS: Tamoxifen-resistant ERα-positive MCF-7 and T47D breast cancer cell lines were established by culturing with gradually increased concentration of 4-hydroxytamoxifen (4-OHT). The effects of NgBR on tamoxifen resistance was determined by depleting NgBR in these cell lines using previously validated small interfering RNA (siRNA). The effects of 4-OHT on cell viability and apoptosis were determined using well-accepted methods such as clonogenic survival assay and Annexin V/propidium iodide staining. The alteration of EGF-stimulated signaling and gene expression was determined by western blot analysis and real-time PCR, respectively. RESULTS: NgBR knockdown with siRNA attenuates EGF-induced phosphorylation of ERα and restores the sensitivity to tamoxifen in ERα-positive breast cancer cells. Mechanistically, our data demonstrated that NgBR knockdown increases the protein levels of p53 and decreases survivin, which is an apoptosis inhibitor. CONCLUSIONS: These results suggested that NgBR is a potential therapeutic target for increasing the sensitivity of ERα-positive breast cancer to tamoxifen. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-018-1028-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-09-12 2018 /pmc/articles/PMC6134690/ /pubmed/30208932 http://dx.doi.org/10.1186/s13058-018-1028-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gao, Pin
Wang, Xiang
Jin, Ying
Hu, Wenquan
Duan, Yajun
Shi, Aiping
Du, Ye
Song, Dong
Yang, Ming
Li, Sijie
Han, Bing
Zhao, Gang
Zhang, Hongquan
Fan, Zhimin
Miao, Qing Robert
Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells
title Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells
title_full Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells
title_fullStr Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells
title_full_unstemmed Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells
title_short Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells
title_sort nogo-b receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134690/
https://www.ncbi.nlm.nih.gov/pubmed/30208932
http://dx.doi.org/10.1186/s13058-018-1028-5
work_keys_str_mv AT gaopin nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT wangxiang nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT jinying nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT huwenquan nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT duanyajun nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT shiaiping nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT duye nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT songdong nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT yangming nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT lisijie nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT hanbing nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT zhaogang nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT zhanghongquan nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT fanzhimin nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells
AT miaoqingrobert nogobreceptorincreasestheresistancetotamoxifeninestrogenreceptorpositivebreastcancercells