Linked Life Data

11059779

Source:http://linkedlifedata.com/resource/pubmed/id/11059779

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2000-11-2
pubmed:abstractText
Androgens are potent differentiation agents that regulate prostate-specific antigen (PSA) gene expression via the androgen receptor (AR) that binds to androgen response elements (AREs) on the PSA gene to initiate transcription. However, in the absence of androgens, PSA gene expression can become elevated. This suggests that either the AR can be activated in the absence of androgen to elevate PSA gene expression through AREs on the PSA gene or that another transcription factor acting on the PSA promoter is stimulated. We have previously shown in vivo that butyrate, a differentiation agent that causes cell cycle arrest, increases serum PSA levels in castrated animals. Therefore, to determine the mechanism of butyrate induction of PSA, we used the LNCaP human prostate cancer cell line. Northern analyses and transfection experiments using a PSA reporter plasmid demonstrated induction of PSA gene expression by butyrate in LNCaP cells. Application of the antiandrogen bicalutamide blocked the induction of PSA mRNA by butyrate, suggesting a mechanism dependent on the AR. Consistent with this conclusion, electromobility shift assays showed increased AR-ARE complex formation with nuclear extracts from butyrate-treated cells. In addition, other reporter gene constructs that contain AREs were also induced by butyrate. Western blot analysis showed an increase in nuclear levels of AR protein in cells exposed to butyrate, whereas whole cell levels remained unchanged, suggesting that butyrate causes nuclear translocation of the AR. Thus, the differentiation agent butyrate causes ligand-independent activation of the AR to increase expression of the differentiation marker PSA in human prostate cancer cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5825-31
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11059779-Androgen Antagonists, pubmed-meshheading:11059779-Anilides, pubmed-meshheading:11059779-Animals, pubmed-meshheading:11059779-Butyrates, pubmed-meshheading:11059779-Cell Differentiation, pubmed-meshheading:11059779-Cell Nucleus, pubmed-meshheading:11059779-Drug Interactions, pubmed-meshheading:11059779-Gene Expression, pubmed-meshheading:11059779-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11059779-Humans, pubmed-meshheading:11059779-Ligands, pubmed-meshheading:11059779-Male, pubmed-meshheading:11059779-Nitriles, pubmed-meshheading:11059779-Promoter Regions, Genetic, pubmed-meshheading:11059779-Prostate-Specific Antigen, pubmed-meshheading:11059779-Prostatic Neoplasms, pubmed-meshheading:11059779-RNA, Messenger, pubmed-meshheading:11059779-Rats, pubmed-meshheading:11059779-Receptors, Androgen, pubmed-meshheading:11059779-Response Elements, pubmed-meshheading:11059779-Tosyl Compounds, pubmed-meshheading:11059779-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Ligand-independent activation of the androgen receptor by the differentiation agent butyrate in human prostate cancer cells.
pubmed:affiliation
Department of Cancer Endocrinology, British Columbia Cancer Agency, Vancouver, Canada. msadar@bccancer.bc.ca
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't