Human estrogen receptor regulation in a yeast model system and studies on receptor agonists and antagonists
An expression system that utilized yeast copper metallothionine promoter and ubiquitin fusion technology to express the human estrogen receptor gene in yeast is described. We have studied the biochemical and transcriptional regulatory properties of the human estrogen receptor. The biochemical proper...
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| Veröffentlicht in: | The Journal of steroid biochemistry and molecular biology 1992-08, Vol.42 (7), p.677-685 |
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| container_issue | 7 |
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| container_title | The Journal of steroid biochemistry and molecular biology |
| container_volume | 42 |
| creator | Lyttle, C.Richard Damian-Matsumura, P. Juul, H. Butt, Tauseef R. |
| description | An expression system that utilized yeast copper metallothionine promoter and ubiquitin fusion technology to express the human estrogen receptor gene in yeast is described. We have studied the biochemical and transcriptional regulatory properties of the human estrogen receptor. The biochemical properties of the yeast expressed receptors are identical to the receptors isolated from human tissue. Estradiol mediated activation of transcription by the receptor was studied by a reporter β-galactosidase gene where expression was under the control of estrogen response elements. Using this expression system and a hyperpermeable yeast strain we have studied the effects of various antiestrogens on the regulation of estrogen receptor function. We demonstrate that tamoxifen and ICI 164,384 are capable of binding to the receptor but neither antiestrogen was able to block the estradiol mediated increase in transcription. In fact, both antiestrogens exerted weak agonist activity in this system. |
| doi_str_mv | 10.1016/0960-0760(92)90108-U |
| format | Article |
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We have studied the biochemical and transcriptional regulatory properties of the human estrogen receptor. The biochemical properties of the yeast expressed receptors are identical to the receptors isolated from human tissue. Estradiol mediated activation of transcription by the receptor was studied by a reporter β-galactosidase gene where expression was under the control of estrogen response elements. Using this expression system and a hyperpermeable yeast strain we have studied the effects of various antiestrogens on the regulation of estrogen receptor function. We demonstrate that tamoxifen and ICI 164,384 are capable of binding to the receptor but neither antiestrogen was able to block the estradiol mediated increase in transcription. 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We have studied the biochemical and transcriptional regulatory properties of the human estrogen receptor. The biochemical properties of the yeast expressed receptors are identical to the receptors isolated from human tissue. Estradiol mediated activation of transcription by the receptor was studied by a reporter β-galactosidase gene where expression was under the control of estrogen response elements. Using this expression system and a hyperpermeable yeast strain we have studied the effects of various antiestrogens on the regulation of estrogen receptor function. We demonstrate that tamoxifen and ICI 164,384 are capable of binding to the receptor but neither antiestrogen was able to block the estradiol mediated increase in transcription. In fact, both antiestrogens exerted weak agonist activity in this system.</description><subject>Amino Acid Sequence</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Cloning, Molecular</subject><subject>Estrogen Antagonists - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors</subject><subject>Humans</subject><subject>Models, Biological</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Receptors, Estrogen - drug effects</subject><subject>Receptors, Estrogen - genetics</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Tamoxifen - pharmacology</subject><subject>Ubiquitins - genetics</subject><subject>Ubiquitins - metabolism</subject><issn>0960-0760</issn><issn>1879-1220</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhi0EKkvhH4DkA0JwSPHHxokvSKiitFIlLt2z5Y_JypDYi8eptP-ebHcpnHryWPO8Y89DyFvOLjjj6jPTijWsU-yjFp8046xvNs_IivedbrgQ7DlZPSIvySvEn4wxKXl3Rs64FFLrdkV-Xc-TTRSwlryFRAt42NVclmI7j7bGnGhM1NI9WKx0ygFGinusMFGbAsU6hwhI839Ru80pYsUHwKb69_6avBjsiPDmdJ6TzdW3u8vr5vbH95vLr7eNl72qTeic772XITitJAPnB1DQSmiF160blHZBexec5wMPupedX_PerftBS8YFk-fkw3HuruTf87KamSJ6GEebIM9oOsmlUi1fwPUR9CUjFhjMrsTJlr3hzBwcm4NAcxBotDAPjs1mib07zZ_dBOFf6Ch16b8_9S16Ow7FJh_xEWvXohPs8PqXIwaLi_sIxaCPkDyEuKisJuT49D_-ACWJmtY</recordid><startdate>19920801</startdate><enddate>19920801</enddate><creator>Lyttle, C.Richard</creator><creator>Damian-Matsumura, P.</creator><creator>Juul, H.</creator><creator>Butt, Tauseef R.</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19920801</creationdate><title>Human estrogen receptor regulation in a yeast model system and studies on receptor agonists and antagonists</title><author>Lyttle, C.Richard ; Damian-Matsumura, P. ; Juul, H. ; Butt, Tauseef R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-d7bc8cc3ddb9630ebcfe6e53e52c95bf69bd9cbdbc1f1d9837c418b48f9301203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Amino Acid Sequence</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Cloning, Molecular</topic><topic>Estrogen Antagonists - pharmacology</topic><topic>Fundamental and applied biological sciences. 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| ispartof | The Journal of steroid biochemistry and molecular biology, 1992-08, Vol.42 (7), p.677-685 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Amino Acid Sequence Biological and medical sciences Blotting, Western Cell receptors Cell structures and functions Cloning, Molecular Estrogen Antagonists - pharmacology Fundamental and applied biological sciences. Psychology Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors Humans Models, Biological Molecular and cellular biology Molecular Sequence Data Receptors, Estrogen - drug effects Receptors, Estrogen - genetics Receptors, Estrogen - metabolism Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Saccharomyces cerevisiae - genetics Tamoxifen - pharmacology Ubiquitins - genetics Ubiquitins - metabolism |
| title | Human estrogen receptor regulation in a yeast model system and studies on receptor agonists and antagonists |
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