Gene amplification of YB-1 in castration-resistant prostate cancer in association with aberrant androgen receptor expression

去势抵抗性前列腺癌中 YB-1 基因扩增与雄激素受体异常表达的关系

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作者:Masaki Shiota, Yohei Sekino, Shigehiro Tsukahara, Tatsuro Abe, Fumio Kinoshita, Kenjiro Imada, Shohei Ueda, Miho Ushijima, Shohei Nagakawa, Takashi Matsumoto, Eiji Kashiwagi, Ario Takeuchi, Junichi Inokuchi, Takeshi Uchiumi, Yoshinao Oda, Masatoshi Eto

Abstract

Although Y-box binding protein-1 (YB-1) is known to be overexpressed in prostate cancer, especially castration-resistant prostate cancer (CRPC), the mechanism of its overexpression remains unclear. We aimed to elucidate the mechanism of YB-1 overexpression in CRPC. Gene amplification in CRPC cells and tissues was examined by public database analysis, and digital PCR. The significance of YB-1 amplification for the YB-1/androgen receptor (AR) axis and prognosis was examined by public database analysis and immunohistochemistry. YB-1 amplification was mainly observed in CRPC tissues by public database analysis and confirmed in CRPC cells and tissues by digital PCR. Expression of YB-1 was increased in CRPC tissues compared with treatment-naïve tissues. Furthermore, YB-1 and phosphorylated YB-1 levels were associated with AR and AR V7 expression levels. Finally, YB-1 amplification was associated with poor outcomes in CRPC. Taken together, the present findings suggest that YB-1 amplification contributes to progression to CRPC through regulation of AR and AR V7 expressions, and that YB-1 is a promising therapeutic target in CRPC.

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