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• W2165854506 abstract "// Nian-Kang Sun 1, 2, * , Shang-Lang Huang 1, * , Pu-Yuan Chang 1 , Hsing-Pang Lu 1 , Chuck C.-K. Chao 1, 3 1 Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan, Republic of China 2 Division of Biomedical Sciences, Chang Gung University of Science and Technology, Taoyuan, 333, Taiwan, Republic of China 3 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan, Republic of China * These two authors contributed equally to this work Correspondence to: Chuck C.-K. Chao, e-mail: cckchao@mail.cgu.edu.tw Received: August 25, 2014      Accepted: October 27, 2014      Published: November 17, 2014 ABSTRACT Taxol is a mitotoxin widely used to treat human cancers, including of the breast and ovary. However, taxol resistance (txr) limits treatment efficacy in human patients. To study chemoresistance in ovarian cancer, we established txr ovarian carcinoma cells derived from the SKOV3 cell lineage. The cells obtained were cross-resistant to other mitotoxins such as vincristine while they showed no resistance to the genotoxin cisplatin. Transcriptomic analysis identified 112 highly up-regulated genes in txr cells. Surprisingly, FK506-binding protein 5 (FKBP5) was transiently up-regulated 100-fold in txr cells but showed decreased expression in prolonged culture. Silencing of FKBP5 sensitized txr cells to taxol, whereas ectopic expression of FKBP5 increased resistance to the drug. Modulation of FKBP5 expression produced similar effects in response to vincristine but not to cisplatin. We observed that a panel of newly identified txr genes was trancriptionally regulated by FKBP5 and silencing of these genes sensitized cells to taxol. Notably, immunoprecipitation experiments revealed that FKBP5 forms a protein complex with the androgen receptor (AR), and this complex regulates the transcriptional activity of both proteins. Furthermore, we found that the Akt kinase pathway is regulated by FKBP5. These results indicate that the FKBP5/AR complex may affect cancer cell sensitivity to taxol by regulating expression of txr genes. Our findings suggest that mitotoxin-based treatment against ovarian cancer should be avoided when the Akt/FKBP5/AR axis is activated." @default.
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• W2165854506 date "2014-11-17" @default.
• W2165854506 modified "2023-10-16" @default.
• W2165854506 title "Transcriptomic profiling of taxol-resistant ovarian cancer cells identifies FKBP5 and the androgen receptor as critical markers of chemotherapeutic response" @default.
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• W2165854506 doi "https://doi.org/10.18632/oncotarget.2654" @default.
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