Abstract:
:There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, heterochromatin protein 1beta (HP1beta), but not HP1alpha or HP1gamma was found to be an AR cofactor. HP1beta interacted with the AR, and enhanced the DNA-binding ability of AR to androgen-responsive element in the prostate-specific antigen enhancer and promoter regions, and to increase the transcription of AR target genes. In prostate cancer (PCa) tissues, HP1beta expressions correlated with Gleason score and tri-methylation levels of histone H3 lysine 9. Silencing of HP1beta suppressed the growth of AR-expressing PCa cells by inducing cell-cycle arrest at the G(1) phase, similar to inhibition of androgen/AR signaling. Furthermore, HP1beta was overexpressed in castration-resistant LNCaP derivative CxR cells, and HP1beta knockdown also suppressed the cell growth in CxR cells. These findings indicate that HP1beta is involved in the proliferation of AR-expressing PCa cells and progression to CRPC as an AR coactivator. Modulation of HP1beta expression or function might be a useful strategy for developing novel therapeutics for PCa, even in CRPC.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Shiota M,Song Y,Yokomizo A,Tada Y,Kuroiwa K,Eto M,Oda Y,Inokuchi J,Uchiumi T,Fujimoto N,Seki N,Naito Sdoi
10.1677/ERC-09-0321subject
Has Abstractpub_date
2010-05-18 00:00:00pages
455-67issue
2eissn
1351-0088issn
1479-6821pii
ERC-09-0321journal_volume
17pub_type
杂志文章abstract::The prognosis remains ill-defined in patients with liver metastases of well-differentiated (WD) digestive endocrine carcinomas (DEC) with high Ki-67 index. The objectives of this study were to determine whether Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in pa...
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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doi:10.1530/ERC-16-0525
更新日期:2017-05-01 00:00:00
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journal_title:Endocrine-related cancer
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