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PMID: 28881721 Published · epublish English Journal Article

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

Oncotarget ·Vol. 8 ·No. 32 ·2017-08-08 ·Pages 52156-52177

Gu Y, Chen T, Li G, Xu C, Xu Z, Zhang J, He K, Zheng L, Guan Z, Su X, Cao J, Teng L

Abstract

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.

Keywords
HER2 beclin 1 breast cancer prognosis tamoxifen resistance
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Gu Yu
Department of Radiation Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai, China. | Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Chen Tianxiang
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Li Guangliang
Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China.
Xu Cong
Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Xu Zhenzhen
Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Zhang Jing
Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
He Kuifeng
Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Zheng Linyan
Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Guan Zhonghai
Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Su Xinyun
Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Cao Jiang
Clinical Research Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Teng Lisong
Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Conflict of Interest

COMPETING INTEREST The authors declare that there are no competing interests.

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Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
DOI
10.18632/oncotarget.11044
Published
2017-08-08
Epub
2016-00-04
Pages
52156-52177
Language
English
Region
United States
NLM ID
101532965
PMCID
PMC5581020
External Links
PubMed source DOI: 10.18632/oncotarget.11044 PMC Full Text View journal details
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