期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 84, 期 -, 页码 28-33出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2016.09.011
关键词
Brachyury; SIRT1; Tamoxifen resistance; Breast cancer
资金
- Natural Science Foundation of China [81372854, 81572591, 81102010]
- Medical Guide Project of Shanghai Science and Technology Committee [15411966200]
- Teaching reform fund of Changhai Hospital [CHJG2015013]
Tamoxifen is effective for treating estrogen receptor-alpha (ER alpha)-positive breast cancers. However, few molecular mediators of tamoxifen resistance have been elucidated. In the present study, we determine the underlying roles of Brachyury in tamoxifen resistance. Loss-and gain-of-function assay are utilized to confirm the oncogenic roles of Brachyury in breast cancer. Compared with the normal MCF10A cells, Brachyury is commonly overexpressed in breast cancer cell lines. Knockdown of Brachyury inhibits tamoxifen resistance, whereas overexpression of Brachyury enhances tamoxifen resistance as demonstrated increased cell viability and reduced cell apoptosis. Mechanistically, we demonstrate for the first time that Brachyury mediates tamoxifen resistance by regulating Sirtuin-1 (SIRT1). Collectively, our data, as a proof of principle, indicate that Brachyury is a candidate marker for predicting the clinical efficacy of tamoxifen and targeting SIRT1 could overcome resistance to tamoxifen in breast cancer cells. (C) 2016 Elsevier Masson SAS. All rights reserved.
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