Abstract | BACKGROUND: METHODS: Gene expression was determined by RT-PCR. The association of AR with UGT2B15/B17 genes was determined by Chromatin immuno-precipitation (CHIP). RNA interference was used to knock-down gene expression. RESULTS: UGT2B15 and B17 genes were not expressed in AR negative prostate cancer cell lines, PC3 and DU145, while they were expressed in AR positive cell lines, LNCaP, LNCaP-abl (an androgen independent LNCaP sub-line), and VCaP. The expression levels of UGT2B15/B17 were up-regulated in LNCaP-abl comparing to those in LNCaP. These results suggest the requirement of AR for the expression of UGT2B15/B17. Treatment with DHT down-regulated the expression of UGT2B15/B17 in LNCaP in a time and dose dependent manner and this down-regulation was competitively antagonized by flutamide and bicalutimide, suggesting a pathway mediated by AR. Further CHIP experiments demonstrated the direct interaction of AR with the promoter regions of UGT2B15/B17 genes. Knocking down AR expression in LNCaP significantly reduced the expression of UGT2B15/B17 and completely inhibited the DHT-induced down-regulation of UGT2B15/B17 genes. CONCLUSIONS: We demonstrated that UGT2B15 and B17 are primary androgen-regulated genes and AR is required for both their basal expression and their androgen-regulated expression.
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Authors | Bo-Ying Bao, Bin-Fay Chuang, Qianben Wang, Oliver Sartor, Steven P Balk, Myles Brown, Philip W Kantoff, Gwo-Shu Mary Lee |
Journal | The Prostate
(Prostate)
Vol. 68
Issue 8
Pg. 839-48
(Jun 01 2008)
ISSN: 0270-4137 [Print] United States |
PMID | 18302198
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | (c) 2008 Wiley-Liss, Inc. |
Chemical References |
- Androgen Receptor Antagonists
- Minor Histocompatibility Antigens
- Receptors, Androgen
- Dihydrotestosterone
- Glucuronosyltransferase
- UDP-glucuronosyltransferase 2B15, human
- UGT2B17 protein, human
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Topics |
- Androgen Receptor Antagonists
- Cell Line, Tumor
- Dihydrotestosterone
(pharmacology)
- Down-Regulation
- Gene Expression
(drug effects)
- Gene Expression Regulation, Enzymologic
- Glucuronosyltransferase
(genetics, metabolism)
- Humans
- Male
- Minor Histocompatibility Antigens
- Neoplasms, Hormone-Dependent
(enzymology, genetics)
- Promoter Regions, Genetic
- Prostatic Neoplasms
(enzymology, genetics)
- RNA Interference
- Receptors, Androgen
(genetics, metabolism)
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