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 Cancerjournal_title
Endocrine-related cancerauthors
Shiota M,Takeuchi A,Song Y,Yokomizo A,Kashiwagi E,Uchiumi T,Kuroiwa K,Tatsugami K,Fujimoto N,Oda Y,Naito Sdoi
10.1530/ERC-11-0017subject
Has Abstractpub_date
2011-07-11 00:00:00pages
505-17issue
4eissn
1351-0088issn
1479-6821pii
ERC-11-0017journal_volume
18pub_type
杂志文章abstract::The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/...
journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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