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イツミ モモエ
逸見 百江 所属 川崎医科大学 医学部 一般教養 自然科学 職種 助教 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Potential Role for YB-1 in Castration-Resistant Prostate Cancer and Resistance to Enzalutamide Through the Androgen Receptor V7. |
| 掲載誌名 | 正式名：Journal of the National Cancer Institute 略 称：J Natl Cancer Inst ISSNコード：14602105/00278874 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 108(7) |
| 著者・共著者 | Masaki Shiota, Naohiro Fujimoto, Kenjiro Imada, Akira Yokomizo, Momoe Itsumi, Ario Takeuchi, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito |
| 発行年月 | 2016/07 |
| 概要 | BACKGROUND:Although androgen deprivation therapy for advanced prostate cancer initially exerts excellent anticancer effects, most prostate cancer treated with androgen deprivation therapy eventually recurs as castration-resistant prostate cancer (CRPC). Although aberrant kinase activation has been proposed as a mechanism of castration resistance, comprehensive kinase profiles in CRPC remain unknown. Therefore, we aimed to elucidate the kinome in CRPC as well as the role of key molecules.METHODS:We utilized a kinome array in androgen-dependent LNCaP and castration-resistant CxR cells. The effect of Y-box binding protein-1 (YB-1) on androgen receptor (AR) expression was examined by quantitative polymerase chain reaction and western blot analysis. The association between polymorphisms in the YB-1 gene determined by genotyping and YB-1 expression evaluated by immunohistochemistry in prostate cancer tissues, as well as outcome in metastatic prostate cancer, were investigated by the Cochran-Armitage test and the Cox proportional hazards model, respectively. All statistical tests were two-sided.RESULTS:One hundred fifty-six of 180 kinase phosphorylation sites, including ERK and RSK, were activated in CRPC cells, leading to increased phosphorylation of YB-1, which is a key molecule in the progression to CRPC. YB-1 signaling regulated AR V7 expression, and YB-1 inhibition augmented the anticancer effect of enzalutamide. Moreover, polymorphism (rs12030724) in the YB-1 gene affected YB-1 expression in 93 prostate cancer tissues (YB-1 positive rate; 14.3% in TT, 40.0% in AT, and 52.9% in AA, P = .04) and associated with probability of progression in 104 metastatic prostate cancer case patients (AT/TT vs AA, hazard ratio = 0.49, 95% confidence interval = 0.32 to 0.77, P = .001).CONCLUSIONS:YB-1 appears to be a promising target to inhibit the development of castration resistance, even at the AR variant-expressing stage. Polymorphism in the YB-1 gene may be a promising predictive |
| DOI | 10.1093/jnci/djw005 |
| PMID | 26857528 |