Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression

Masaki Shiota, Ario Takeuchi, Yoo Hyun Song, Akira Yokomizo, Eiji Kashiwagi, Takeshi Uchiumi, Kentaro Kuroiwa, Katsunori Tatsugami, Naohiro Fujimoto, Yoshinao Oda, Seiji Naito

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

The androgen receptor (AR) is well known to play a central role in the pathogenesis of prostate cancer (PCa). In several studies, AR was overexpressed in castration-resistant PCa (CRPC). However, the mechanism of AR overexpression in CRPC is not fully elucidated. Y-box binding protein-1 (YB-1) is a pleiotropic transcription factor that is upregulated in CPRC. We aimed to elucidate the role of YB-1 in castration resistance of PCa and identify therapeutic potential of targeting YB-1. Using immunohistochemistry, we found that nuclear YB-1 expression significantly correlated with the Gleason score and AR expression in PCa tissues. In PCa cells, YB-1 regulated AR expression at the transcriptional level. Furthermore, YB-1 expression and nuclear localization were upregulated in CRPC cells. Overexpression of AR, as well as YB-1, conferred castrationresistant growth in LNCaP and 22Rv1 cells. Conversely, knocking down YB-1 resulted in suppressed cell growth and induced apoptosis, which was more efficient than knocking down AR in LNCaP cells. In other types of PCa cells, such as CRPC cells, knocking down YB-1 resulted in a significant reduction of cell growth. In conclusion, these findings suggested that YB-1 induces castration resistance in androgen-dependent PCa cells via AR expression. Thus, YB-1 may be a promising therapeutic target for PCa, as well as CRPC.

Original languageEnglish
Pages (from-to)505-517
Number of pages13
JournalEndocrine-Related Cancer
Volume18
Issue number4
DOIs
Publication statusPublished - Aug 2011

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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