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

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.