Oncotarget

Research Papers:

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

Yu Gu, Tianxiang Chen, Guangliang Li, Cong Xu, Zhenzhen Xu, Jing Zhang, Kuifeng He, Linyan Zheng, Zhonghai Guan, Xinyun Su, Jiang Cao and Lisong Teng _

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Oncotarget. 2017; 8:52156-52177. https://doi.org/10.18632/oncotarget.11044

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Abstract

Yu Gu1,2, Tianxiang Chen3, Guangliang Li4, Cong Xu2, Zhenzhen Xu2, Jing Zhang2, Kuifeng He2, Linyan Zheng2, Zhonghai Guan2, Xinyun Su2, Jiang Cao5 and Lisong Teng2

1Department of Radiation Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai, China

2Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China

3Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

4Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China

5Clinical Research Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China

Correspondence to:

Lisong Teng, email: lsteng@zju.edu.cn

Keywords: breast cancer, tamoxifen resistance, prognosis, beclin 1, HER2

Received: September 16, 2015    Accepted: June 29, 2016    Published: August 04, 2016

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.


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