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

2020 ◽  
Vol 112 (1) ◽  
pp. 323-330
Author(s):  
Masaki Shiota ◽  
Yohei Sekino ◽  
Shigehiro Tsukahara ◽  
Tatsuro Abe ◽  
Fumio Kinoshita ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Gene Amplification ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Increased androgen receptor transcription: a cause of castration-resistant prostate cancer and a possible therapeutic target

2011 ◽  
Vol 47 (1) ◽  
pp. R25-R41 ◽  
Author(s):  
Masaki Shiota ◽  
Akira Yokomizo ◽  
Seiji Naito
Keyword(s):  
Prostate Cancer ◽  
Transcription Factors ◽  
Androgen Receptor ◽  
Gene Amplification ◽  
Transcriptional Control ◽  
Therapeutic Potential ◽  
Mrna Level ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Carcinogenesis ◽  
Castration Resistant

Few effective therapies exist for the treatment of castration-resistant prostate cancer (CRPC). Recent evidence suggests that CRPC may be caused by augmented androgen/androgen receptor (AR) signaling, generally involving AR overexpression. Aberrant androgen/AR signaling associated with AR overexpression also plays a key role in prostate carcinogenesis. Although AR overexpression could be attributed to gene amplification, only 10–20% of CRPCs exhibit AR gene amplification, and aberrant AR expression in the remaining instances of CRPC is thought to be attributed to transcriptional, translational, and post-translational mechanisms. Overexpression of AR at the protein level, as well as the mRNA level, has been found in CRPC, suggesting a key role for transcriptional regulation of AR expression. Since the analysis of the AR promoter region in the 1990s, several transcription factors have been reported to regulate AR transcription. In this review, we discuss the molecules involved in the control of AR gene expression, with emphasis on its transcriptional control by transcription factors in prostate cancer. We also consider the therapeutic potential of targeting AR expression.

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

2011 ◽  
Vol 18 (4) ◽  
pp. 505-517 ◽  
Author(s):  
Masaki Shiota ◽  
Ario Takeuchi ◽  
YooHyun Song ◽  
Akira Yokomizo ◽  
Eiji Kashiwagi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Therapeutic Potential ◽  
Binding Protein ◽  
Receptor Expression ◽  
Transcriptional Level ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Castration Resistant

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.

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