Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 331, Issue 1, Pages 57-65Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2010.08.008
Keywords
Androgen receptor; VCaP; Prostate cancer cell; Antiandrogen; Gene expression; Chromatin immunoprecipitation (ChIP)
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Funding
- Academy of Finland
- Finnish Cancer Foundation
- Sigrid Juselius Foundation
- Ida Montini Foundation
- North Savo Cancer Foundation
- Kuopio University Hospital
- Finnish Medical Foundation
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Androgen receptor (AR) is overexpressed in a majority of castration-resistant prostate cancers, but most of the cell model studies addressing AR function have been conducted in LNCaP prostate cancer cells expressing unamplified AR levels. Here, we have compared the responses of various types of AR ligands towards a pattern of AR target genes and chromatin binding sites in Vertebral-Cancer of the Prostate (VCaP) cells and LNCaP cells. In keeping with the AR gene amplification in VCaP cells, our analyses show that these cells contain >= 10-fold receptor mRNA and protein than LNCaP cells. Loading of the agonist-occupied AR onto chromatin regulatory sites and expression of several AR target genes, including their basal expression, were stronger in VCaP cells than LNCaP cells. Bicalutamide displayed a trend towards agonism in VCaP cells. Bicalutamide also evoked AR-chromatin interaction, whereas diarylthiohydantoin antiandrogen RD162 was inert with this respect both in VCaP and LNCaP cells. These results support the notion that the AR protein level translates into augmented occupancy of AR-regulated enhancers and target gene activity in prostate cancer cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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