title: A mutation in beta-tubulin and a sustained dependence on androgen receptor signalling in a newly established docetaxel-resistant prostate cancer cell line.
abstract: The mechanisms of docetaxel resistance in PC (prostate cancer) are unclear because of the lack of suitable experimental models, and no effective treatment exists for docetaxel-resistant PC. We established a docetaxel-resistant cell line, LNDCr, from an androgen-refractory PC cell line, LNCaP-hr, by intermittent exposure to docetaxel in vitro. The LNDCr cells harboured an F270I mutation in class I beta-tubulin, and demonstrated impaired tubulin polymerization by docetaxel. AR signalling was sustained in LNDCr cells, and AR knockdown suppressed the growth of LNDCr cells. These results suggest that an acquired mutation in beta-tubulin is associated with docetaxel resistance in PC and that a novel AR-targeted therapy is effective for docetaxel-resistant PC.
authors: Pharmacology Research Laboratories, Takeda Pharmaceutical Company Limited, Tsukuba, Japan. Hara_Takahito@takeda.co.jp
authors: Takahito
authors: T
authors: Hara
authors: Kazutaka
authors: K
authors: Ushio
authors: Mayumi
authors: M
authors: Nishiwaki
authors: Jin
authors: J
authors: Kouno
authors: Hideo
authors: H
authors: Araki
authors: Yukiko
authors: Y
authors: Hikichi
authors: Masahiko
authors: M
authors: Hattori
authors: Yumi
authors: Y
authors: Imai
authors: Masuo
authors: M
authors: Yamaoka
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D043823:Taxoids / Q000494:pharmacology*; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel