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Breast Cancer Research
Published in: Breast Cancer Research 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Pin Gao, Xiang Wang, Ying Jin, Wenquan Hu, Yajun Duan, Aiping Shi, Ye Du, Dong Song, Ming Yang, Sijie Li, Bing Han, Gang Zhao, Hongquan Zhang, Zhimin Fan, Qing Robert Miao

Published in: Breast Cancer Research | Issue 1/2018

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Abstract

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.
Appendix
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Metadata
Title
Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells
Authors
Pin Gao
Xiang Wang
Ying Jin
Wenquan Hu
Yajun Duan
Aiping Shi
Ye Du
Dong Song
Ming Yang
Sijie Li
Bing Han
Gang Zhao
Hongquan Zhang
Zhimin Fan
Qing Robert Miao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2018
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-018-1028-5

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