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https://hdl.handle.net/2440/9696
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DC Field | Value | Language |
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dc.contributor.author | Jia, L. | - |
dc.contributor.author | Kim, J. | - |
dc.contributor.author | Shen, H. | - |
dc.contributor.author | Clark, P. | - |
dc.contributor.author | Tilley, W. | - |
dc.contributor.author | Coetzee, G. | - |
dc.date.issued | 2003 | - |
dc.identifier.citation | Molecular Cancer Research, 2003; 1(5):385-392 | - |
dc.identifier.issn | 1541-7786 | - |
dc.identifier.issn | 1557-3125 | - |
dc.identifier.uri | http://hdl.handle.net/2440/9696 | - |
dc.description.abstract | Ligand-activated androgen receptors (ARs) occupy target genes and recruit histone modifiers that influence transcriptional competency. In LNCaP prostate cancer cells, the natural ligand 5alpha-dihydrotestosterone (DHT) activates transiently transfected AR-responsive promoter constructs; concurrent treatment with the protein kinase A activator forskolin enhanced AR stimulation induced by DHT. Additional treatment with the cytokine IL-6, purportedly an AR activator, markedly inhibited receptor activity. To assess AR activity on natural chromatin-integrated promoters/enhancers, we determined AR occupancy of the endogenous prostate specific antigen (PSA) promoter/enhancer as well as PSA expression in LNCaP cells treated with DHT; AR occupancy of the PSA enhancer was rapid (within 1 h of stimulation), robust (10-fold over background), and sustained (8-16 h). In contrast, AR occupancy of the PSA promoter was only increased by 2-fold. Histone H3 acetylation at both the enhancer and promoter was evident 1-2 h after DHT treatment. Detectable pre- and mature PSA mRNA levels appeared after 1 and 6 h treatment, respectively. Substantial qualitative and quantitative differences in PSA expression and AR occupancy of the PSA enhancer were observed when DHT-induced and ligand-independent activations of the AR were compared; forskolin stimulated PSA mRNA and protein expression, whereas IL-6 inhibited both DHT- and forskolin-stimulated expression. IL-6 did not diminish DHT-dependent AR occupancy of the PSA enhancer but inhibited CBP/p300 recruitment, histone H3 acetylation, and cell proliferation. These findings provide a contextual framework for interpreting the contribution of non-steroidal activation of the AR to signaling in vivo, and have implications for prostate cancer cell growth. | - |
dc.description.statementofresponsibility | Li Jia, Joshua Kim, Howard Shen, Peter E. Clark, Wayne D. Tilley, and Gerhard A. Coetzee | - |
dc.language.iso | en | - |
dc.publisher | Amer Assoc Cancer Research | - |
dc.rights | © 2003 American Association for Cancer Research | - |
dc.source.uri | http://mcr.aacrjournals.org/content/1/5/385.abstract? | - |
dc.subject | prostate cancer | - |
dc.subject | androgen receptor | - |
dc.subject | transcription | - |
dc.subject | IL-6 | - |
dc.subject | prostate specific antigen | - |
dc.title | Androgen receptor activity at the prostate specific antigen locus: Steroidal and non-steroidal mechanisms | - |
dc.type | Journal article | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Tilley, W. [0000-0003-1893-2626] | - |
Appears in Collections: | Aurora harvest Medicine publications |
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