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• W1856950927 abstract "// Jie Ming 1, * , Shengnan Ruan 1, * , Mengyi Wang 1 , Dan Ye 1 , Ningning Fan 2 , Qingyu Meng 3 , Bo Tian 4, 5 , Tao Huang 1 1 Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China 2 Department of Breast and Thyroid Surgery, Luoyang Central Hospital, Zhengzhou University, Luoyang, Henan 471009, P.R. China 3 Department of Radiation Oncology, Peking Union Medical College hospital, Beijing 100730, P.R. China 4 Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China 5 Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China * These authors have contributed equally to this work Correspondence to: Jie Ming, e-mail: mingjiewh@126.com Tao Huang, e-mail: huangtaowh@163.com Keywords: STF-080310, tamoxifen, breast cancer, IRE1/XBP1 Received: May 21, 2015      Accepted: September 23, 2015      Published: October 19, 2015 ABSTRACT Recent studies show that the unfolded protein response (UPR) within the endoplasmic reticulum is correlated with breast cancer drug resistance. In particular, human X-box binding protein-1(XBP1), a transcription factor which participates in UPR stress signaling, is reported to correlate with poor clinical responsiveness to tamoxifen. In this study, we develop a tamoxifen-resistant MCF-7 cell line by treating the cell line with low concentration of tamoxifen, and we find that XBP1 is indeed up-regulated at both the mRNA and protein levels compared to normal MCF-7 cells. STF-083010, a novel inhibitor which specifically blocks the XBP1 splicing, reestablishes tamoxifen sensitivity to resistant MCF-7 cells. Moreover, co-treatment with STF-083010 and tamoxifen can significantly delay breast cancer progression in a xenograft mammary tumor model. We next investigate the expression of XBP1s in over 170 breast cancer patients’ samples and the results demonstrate that XBP1s expression level is highly correlated with overall survival in the ER + subgroup, but not in the ER − subgroup, suggesting a potential therapeutic application of XBP1 inhibitors in ER + breast cancer treatment." @default.
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• W1856950927 date "2015-10-19" @default.
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• W1856950927 title "A novel chemical, STF-083010, reverses tamoxifen-related drug resistance in breast cancer by inhibiting IRE1/XBP1" @default.
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• W1856950927 doi "https://doi.org/10.18632/oncotarget.5827" @default.
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