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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhang, Buchang Zhu, Lin Ling, Youguo Zhong, Hui Xu, Quanbin Wei, Congwen Ge, Xiaoxing Xu, Changzhi Cao, Ye Song, Ting Wang, Qiang Zhang, Yanhong Yang, Xiaoli Hu, Chengjin Li, Jia He, Xiang Guan, Kai Yan, Hui Bian, Xiu-wu Ma, Shengli Zheng, Zirui Cao, Yuan Tai, Yanhong |
| Description | Author Affiliation: Wei C ( State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100850, China.); |
| Abstract | Resistance to antiestrogens is one of the major challenges in breast cancer treatment. Although phosphorylation of estrogen receptor (ER ) is an important factor in endocrine resistance, the contributions of specific kinases in endocrine resistance are still not fully understood. Here, we report that an important innate immune response kinase, the IκB kinase-related TANK-binding kinase 1 (TBK1), is a crucial determinant of resistance to tamoxifen therapies. We show that TBK1 increases ER transcriptional activity through phosphorylation modification of ER at the Ser-305 site. Ectopic TBK1 expression impairs the responsiveness of breast cancer cells to tamoxifen. By studying the specimens from patients with breast cancer, we find a strong positive correlation of TBK1 with ER , ER Ser-305, and cyclin D1. Notably, patients with tumors highly expressing TBK1 respond poorly to tamoxifen treatment and show high potential for relapse. Therefore, our findings suggest that TBK1 contributes to tamoxifen resistance in breast cancer via phosphorylation modification of ER . |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Breast Neoplasms Metabolism Drug Resistance, Neoplasm Drug Effects Protein-Serine-Threonine Kinases Tamoxifen Pharmacology Drug Therapy Genetics Pathology Cell Line, Tumor Cyclin D1 Estrogen Receptor Alpha Immunity, Innate Kaplan-Meier Estimate Phosphorylation Phosphoserine Protein Binding Therapeutic Use Transcription, Genetic Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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