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rdf:type |
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lifeskim:mentions |
umls-concept:C0014406,
umls-concept:C0014930,
umls-concept:C0017262,
umls-concept:C0034804,
umls-concept:C0035820,
umls-concept:C0036025,
umls-concept:C0086418,
umls-concept:C0086597,
umls-concept:C0205210,
umls-concept:C0205314,
umls-concept:C0220825,
umls-concept:C0441655,
umls-concept:C0596902,
umls-concept:C0679622,
umls-concept:C1171362,
umls-concept:C1515670
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pubmed:issue |
3
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pubmed:dateCreated |
1997-7-24
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pubmed:abstractText |
The effectiveness of anti-estrogens in treating estrogen-dependent diseases is limited by the acquired resistance of some diseases to anti-estrogens. This effect could occur by the export of anti-estrogens by cell membrane transport proteins. To study this phenomenon we have expressed human estrogen receptor (hER) and an estrogen-sensitive reporter in wild-type yeast and two transport-defective strains. In the wild-type strain, the most effective anti-estrogen was nafoxidine. 4-Hydroxy tamoxifen and clomiphene were inactive whereas tamoxifen had significant inhibitory activity in the wild-type strain. Using a strain missing the ABC-cassette transporter Snq2, clomiphene had anti-estrogenic activity. 4-Hydroxy tamoxifen had anti-estrogenic activity only in yeast lacking the transporter Pdr5. Whole cell binding assays indicated that 4-hydroxy tamoxifen is exported by Pdr5. Environmental chemicals such as polychlorinated biphenyls function as partial estrogens and anti-estrogens in yeast. In the absence of Pdr5 or Snq2, the estrogenic activity of 4-hydroxy, 2',4',6'-trichloro biphenyl (3-PCB) was substantially reduced in comparison to its activity in the wild-type strain. Interestingly, the antiestrogenic activity of 3-PCB was equivalent in the wild-type and transporter-defective strains. Our results suggest a novel role for ABC-cassette transporters in regulating the activity of clinical and environmental anti-estrogens.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,4',5-trichlorobiphenyl,
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxytamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Clomiphene,
http://linkedlifedata.com/resource/pubmed/chemical/Estriol,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Fungal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nafoxidine,
http://linkedlifedata.com/resource/pubmed/chemical/PDR5 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Polychlorinated Biphenyls,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SNQ2 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
235
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
669-74
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9207217-ATP-Binding Cassette Transporters,
pubmed-meshheading:9207217-Clomiphene,
pubmed-meshheading:9207217-Cloning, Molecular,
pubmed-meshheading:9207217-Estriol,
pubmed-meshheading:9207217-Estrogen Antagonists,
pubmed-meshheading:9207217-Fungal Proteins,
pubmed-meshheading:9207217-Gene Deletion,
pubmed-meshheading:9207217-Genes, Reporter,
pubmed-meshheading:9207217-Humans,
pubmed-meshheading:9207217-Membrane Proteins,
pubmed-meshheading:9207217-Nafoxidine,
pubmed-meshheading:9207217-Polychlorinated Biphenyls,
pubmed-meshheading:9207217-Receptors, Estrogen,
pubmed-meshheading:9207217-Recombinant Fusion Proteins,
pubmed-meshheading:9207217-Saccharomyces cerevisiae,
pubmed-meshheading:9207217-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:9207217-Tamoxifen,
pubmed-meshheading:9207217-beta-Galactosidase
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pubmed:year |
1997
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pubmed:articleTitle |
Evaluation of clinical and environmental anti-estrogens with human estrogen receptor expressed in Saccharomyces cerevisiae: a novel role for ABC-cassette transporters in mediating anti-estrogenic activity.
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pubmed:affiliation |
Department of Environmental Health Sciences, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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