A mutation in beta-tubulin and a sustained dependence on androgen receptor signalling in a newly established docetaxel-resistant prostate cancer cell line
| Autor: | Masuo Yamaoka, Hideo Araki, Takahito Hara, Mayumi Nishiwaki, Yukiko Hikichi, Jin Kouno, Yumi Imai, Kazutaka Ushio, Masahiko Hattori |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Antineoplastic Agents Docetaxel Pharmacology urologic and male genital diseases medicine.disease_cause Prostate cancer Tubulin Cell Line Tumor medicine Humans RNA Small Interfering neoplasms Mutation Gene knockdown biology Chemistry organic chemicals Prostatic Neoplasms Cell Biology General Medicine medicine.disease In vitro Androgen receptor Cell culture Drug Resistance Neoplasm Receptors Androgen Cancer research biology.protein RNA Interference Taxoids therapeutics medicine.drug Signal Transduction |
| Zdroj: | Cell biology international. 34(2) |
| ISSN: | 1095-8355 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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