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The role of testicular nuclear receptor 4 in chemo-resistance of docetaxel in castration-resistant prostate cancer

Cancer Gene Therapy volume 21, pages 411–415 (2014)Cite this article

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Abstract

Docetaxel-based therapy is one of the first-line options for castration-resistant prostate cancer (CRPC). However, a large proportion of CRPC patients show different extents of docetaxel resistance. The current study aims to investigate the role of testicular nuclear receptor 4 (TR4) in docetaxel resistance in CRPC. TR4 expression level in prostate biopsy samples from CRPC patients treated with docetaxel was measured by immunohistochemistry (IHC). Alternation of TR4 expression in prostate cancer (PCa) cell line PC3 was applied to find out the influence of TR4 on half-maximal inhibitory concentration (IC50), cell viability and cell apoptosis. Patients who failed to achieve prostate-specific antigen (PSA) response (<50% PSA reduction from baseline) after docetaxel-based chemotherapy had a comparatively higher TR4 expression than those who achieved PSA response (⩾50% PSA reduction from baseline). Knocking down TR4 in PC3 cells led to a lower IC50 dose, poorer cell viability and more cell apoptosis when treated with docetaxel, whereas overexpression of TR4 in PC3 led to a higher IC50 dose, better cell viability and less cell apoptosis. TR4 enhances the chemo-resistance of docetaxel in CRPC. It may serve as a biomarker to determine the prognosis of docetaxel-based therapy and as a potential therapy target to combine with docetaxel to better suppress CRPC.

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Acknowledgements

This study is funded by The Qianjiang Talents Project of Zhejiang Province (grant number: 2011R10039), The Natural Science Foundation of Zhejiang Province (grant number: Y2110446), The National Natural Science Foundation of China (grant number: 30973001), Medical Platform Key Funding of Zhejiang Province (2014ZDA011), Medical General project of Zhejiang Province (2014KYB134) and The National Basic Research Program (973) of China (grant number: 2012CB518304).

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Authors and Affiliations

  1. Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

    B Chen, S Yu, X Ding, C Jing, L Xia, M Wang, E Matro, F Rehman, G Li & C Chang

  2. Department of Urology, Chawnshang Chang Sex Hormone Research Center, The 2nd affiliated hospital of Tianjin Medical University, Tianjin, China

    Y Niu

  3. Departments of Pathology, George Whipple Lab for Cancer Research, Urology and Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA

    C Chang

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  1. B Chen
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  2. S Yu
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  3. X Ding
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  4. C Jing
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  5. L Xia
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  6. M Wang
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  7. E Matro
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  8. F Rehman
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  9. Y Niu
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  10. G Li
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  11. C Chang
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Correspondence to G Li.

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Chen, B., Yu, S., Ding, X. et al. The role of testicular nuclear receptor 4 in chemo-resistance of docetaxel in castration-resistant prostate cancer. Cancer Gene Ther 21, 411–415 (2014). https://doi.org/10.1038/cgt.2014.41

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  • DOI: https://doi.org/10.1038/cgt.2014.41

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