title: The role of testicular nuclear receptor 4 in chemo-resistance of docetaxel in castration-resistant prostate cancer.
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.
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Jing
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: E
authors.initials: E
authors.lastname: Matro
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Rehman
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Department of Urology, The 2nd affiliated hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.affiliation: 1] Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China [2] George Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D016086:Lentivirus / Q000235:genetics; D008297:Male; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2 / Q000235:genetics* / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D014161:Transduction, Genetic
chemical_list: D000970:Antineoplastic Agents; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen
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