期刊
CANCER LETTERS
卷 440, 期 -, 页码 54-63出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.09.030
关键词
BTF3; ER alpha; ER plus breast cancer; PI3K alpha inhibition
类别
资金
- National Natural Science Foundation of China [81472447, 81672575, 81372853, 81572586]
- Liaoning Provincial Climbing Scholars Supporting Program of China
- Liaoning Provincial Science and Technology Program for Oversea Talents
- Provincial Natural Science Foundation of Liaoning [2014023002, 2015020316]
- Liaoning Provincial Key Basic Research Program for Colleges and Universities [LZ2017002]
Selective phosphatidylinositol 3 kinase (PI3K) inhibitors are being actively tested in clinical trials for ER alpha-positive (ER +) breast cancer due to the presence of activating PIK3CA mutations. However, recent studies have revealed that increased ER alpha transcriptional activity limits the efficacy of PI3K inhibitor monotherapy for ER + breast cancers. Herein, we report the identification of BTF3 as an oncogenic transcription factor that regulates ER alpha expression in luminal breast cancers. Our TCGA analysis reveals high expression levels of BTF3 in luminal/ER + breast cancer and cell line models harboring ERa overexpression. Concordantly, BTF3 expression is highly and strongly associated with ESR1 expression in multiple breast cancer cohorts. We further show that BTF3 promotes the proliferation, survival and migration of ER + breast cancer cells by modulating ESR1 expression and ER alpha-dependent transcription. Moreover, BTF3 knockdown sensitizes ER + breast cancer cells to the PI3K alpha inhibitor BYL-719 in both in vitro and in vivo models. Together, our findings highlight a novel role of BTF3 in modulation of ER alpha-dependent transcriptional activity and its potential as a predictive marker for the response to PI3K-targeted therapy in ER + breast cancer.
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