We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Androgen receptor level controlled by a suppressor complex lost in an androgen-independent prostate cancer cell line.
- Authors
Wang, Long G; Ossowski, Liliana; Ferrari, Anna C
- Abstract
Androgen receptor (AR) overexpression is one of the characteristics of prostate cancer (PC) that progresses to hormone independence. An androgen-independent (AI) derivative, with much higher AR-mRNA and protein levels than the parental LNCaP cell line, whose proliferation was androgen dependent (AD), was used to explore the mechanism of AR overexpression. We found that a suppressor element (ARS), previously identified in mouse AR and located in the 5'-untranslated region of human AR gene, malfunctions in AI cells. Transfection of constructs that included ARS element into AD cells reduced the transactivating activities of both AR promoter and a heterologous SV40 promoter. The deletion of ARS resulted in an eightfold increase in AR-promoter activity in AD cells, but had no effect in AI cells. Moreover, the nuclear extracts of AD cells contained proteins that produced a specific, ARS-binding complex, while this complex appeared to have been lost from AI cells. Most importantly, treatment of AI cells with a demethylating agent or histone deacetylase inhibitors restored the lost ARS-binding complex. The restoration of the complex coincided with a reduced expression of AR-mRNA and protein and a reduced rate of AR-gene transcription, determined by nuclear run-on experiment. Thus, epigenetic transcriptional silencing of the suppressor protein(s) may be responsible for AR overexpression in AI cells, and its reversal in hormone-independent PC may normalize AR levels and restore their hormone dependence.Oncogene (2004) 23, 5175-5184. doi:10.1038/sj.onc.1207654 Published online 24 May 2004
- Publication
Oncogene, 2004, Vol 23, Issue 30, p5175
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207654