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

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 castration-resistant 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.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Shiota M,Takeuchi A,Song Y,Yokomizo A,Kashiwagi E,Uchiumi T,Kuroiwa K,Tatsugami K,Fujimoto N,Oda Y,Naito S

doi

10.1530/ERC-11-0017

subject

Has Abstract

pub_date

2011-07-11 00:00:00

pages

505-17

issue

4

eissn

1351-0088

issn

1479-6821

pii

ERC-11-0017

journal_volume

18

pub_type

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