Source:http://linkedlifedata.com/resource/pubmed/id/16107550
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-10-5
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pubmed:abstractText |
2,4-Dichlorophenoxyacetic acid (2,4-D) and its metabolite 2,4-dichlorophenol (DCP) are used extensively in agriculture as herbicides, and are suspected of potential endocrine disruptor activity. In a previous study, we showed that these compounds exhibited synergistic androgenic effects by co-treatment with testosterone in the Hershberger assay. To elucidate the mechanisms of the synergistic effects of these compounds on the androgenicity of testosterone, the androgenic action of 2,4-D and DCP was characterized using a mammalian detection system in prostate cancer cell lines. In in vitro assay systems, while 2,4-D or DCP alone did not show androgenic activity, 2,4-D or DCP with 5alpha-dihydroxytestosterone (DHT) exhibited synergistic androgenic activities. Co-treatment of 10 nM 2,4-D or DCP with 10 nM DHT was shown to stimulate the cell proliferation by 1.6-fold, compared to 10 nM DHT alone. In addition, in transient transfection assays, androgen-induced transactivation was also increased to a maximum of 32-fold or 1.28-fold by co-treatment of 2,4-D or DCP with DHT, respectively. However, 2,4-D and DCP exerted no effects on either mRNA or protein levels of AR. In a competitive AR binding assay, 2,4-D and DCP inhibited androgen binding to AR, up to 50% at concentrations of approximately 0.5 microM for both compounds. The nuclear translocation of green fluorescent protein-AR fusion protein in the presence of DHT was promoted as the result of the addition of 2,4-D and DCP. Collectively, these results that 2,4-D and DCP enhanced DHT-induced AR transcriptional activity might be attributable, at least in part, to the promotion of AR nuclear translocation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,4-Dichlorophenoxyacetic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/2,4-dichlorophenol,
http://linkedlifedata.com/resource/pubmed/chemical/Androgens,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorophenols,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydrotestosterone,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Androgen
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1096-6080
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
52-9
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pubmed:dateRevised |
2010-9-17
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pubmed:meshHeading |
pubmed-meshheading:16107550-2,4-Dichlorophenoxyacetic Acid,
pubmed-meshheading:16107550-Androgens,
pubmed-meshheading:16107550-Cell Line, Tumor,
pubmed-meshheading:16107550-Cell Proliferation,
pubmed-meshheading:16107550-Chlorophenols,
pubmed-meshheading:16107550-Dihydrotestosterone,
pubmed-meshheading:16107550-Dose-Response Relationship, Drug,
pubmed-meshheading:16107550-Drug Synergism,
pubmed-meshheading:16107550-Humans,
pubmed-meshheading:16107550-Male,
pubmed-meshheading:16107550-Prostatic Neoplasms,
pubmed-meshheading:16107550-RNA, Messenger,
pubmed-meshheading:16107550-RNA, Neoplasm,
pubmed-meshheading:16107550-Receptors, Androgen,
pubmed-meshheading:16107550-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16107550-Transcriptional Activation
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pubmed:year |
2005
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pubmed:articleTitle |
Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate cancer cells.
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pubmed:affiliation |
School of Life Sciences & Biotechnology, Korea University, 1, 5-Ka, Anam-dong, Sungbuk-ku, Seoul 136-701, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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