3-methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor α
3-Methylcholanthrene (3MC) is an aryl hydrocarbon receptor (AhR) agonist, and it has been reported that 3MC induces estrogenic activity through AhR-estrogen receptor alpha (ER alpha) interactions. In this study, we used 3MC and 3,3',4,4',5-pentachlorobiphenyl (PCB) as prototypical AhR liga...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2006-02, Vol.66 (4), p.2459-2467 |
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| creator | ABDELRAHIM, Maen ARIAZI, Eric JORDAN, V. Craig SAFE, Stephen KIM, Kyounghyun KHAN, Shaheen BARHOUMI, Rola BURGHARDT, Robert SHENGXI LIU HILL, Denise FINNELL, Richard WLODARCZYK, Bogdan |
| description | 3-Methylcholanthrene (3MC) is an aryl hydrocarbon receptor (AhR) agonist, and it has been reported that 3MC induces estrogenic activity through AhR-estrogen receptor alpha (ER alpha) interactions. In this study, we used 3MC and 3,3',4,4',5-pentachlorobiphenyl (PCB) as prototypical AhR ligands, and both compounds activated estrogen-responsive reporter genes/gene products (cathepsin D) in MCF-7 breast cancer cells. The estrogenic responses induced by these AhR ligands were inhibited by the antiestrogen ICI 182780 and by the transfection of a small inhibitory RNA for ER alpha but were not affected by the small inhibitory RNA for AhR. These results suggest that 3MC and PCB directly activate ER alpha, and this was confirmed in a competitive ER alpha binding assay and in a fluorescence resonance energy transfer experiment in which PCB and 3MC induced CFP-ER alpha/YFP-ER alpha interactions. In a chromatin immunoprecipitation assay, PCB and 3MC enhanced ER alpha (but not AhR) association with the estrogen-responsive region of the pS2 gene promoter. Moreover, in AhR knockout mice, 3MC increased uterine weights and induced expression of cyclin D1 mRNA levels. These results show that PCB and 3MC directly activate ER alpha-dependent transactivation and extend the number of ligands that activate both AhR and ER alpha. |
| doi_str_mv | 10.1158/0008-5472.CAN-05-3132 |
| format | Article |
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Craig ; SAFE, Stephen ; KIM, Kyounghyun ; KHAN, Shaheen ; BARHOUMI, Rola ; BURGHARDT, Robert ; SHENGXI LIU ; HILL, Denise ; FINNELL, Richard ; WLODARCZYK, Bogdan</creator><creatorcontrib>ABDELRAHIM, Maen ; ARIAZI, Eric ; JORDAN, V. Craig ; SAFE, Stephen ; KIM, Kyounghyun ; KHAN, Shaheen ; BARHOUMI, Rola ; BURGHARDT, Robert ; SHENGXI LIU ; HILL, Denise ; FINNELL, Richard ; WLODARCZYK, Bogdan</creatorcontrib><description>3-Methylcholanthrene (3MC) is an aryl hydrocarbon receptor (AhR) agonist, and it has been reported that 3MC induces estrogenic activity through AhR-estrogen receptor alpha (ER alpha) interactions. In this study, we used 3MC and 3,3',4,4',5-pentachlorobiphenyl (PCB) as prototypical AhR ligands, and both compounds activated estrogen-responsive reporter genes/gene products (cathepsin D) in MCF-7 breast cancer cells. The estrogenic responses induced by these AhR ligands were inhibited by the antiestrogen ICI 182780 and by the transfection of a small inhibitory RNA for ER alpha but were not affected by the small inhibitory RNA for AhR. These results suggest that 3MC and PCB directly activate ER alpha, and this was confirmed in a competitive ER alpha binding assay and in a fluorescence resonance energy transfer experiment in which PCB and 3MC induced CFP-ER alpha/YFP-ER alpha interactions. In a chromatin immunoprecipitation assay, PCB and 3MC enhanced ER alpha (but not AhR) association with the estrogen-responsive region of the pS2 gene promoter. Moreover, in AhR knockout mice, 3MC increased uterine weights and induced expression of cyclin D1 mRNA levels. These results show that PCB and 3MC directly activate ER alpha-dependent transactivation and extend the number of ligands that activate both AhR and ER alpha.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-05-3132</identifier><identifier>PMID: 16489053</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Binding, Competitive ; Biological and medical sciences ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Cyclin D1 - biosynthesis ; Cyclin D1 - genetics ; Dimerization ; Estradiol - pharmacology ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - metabolism ; Female ; Fluorescence Resonance Energy Transfer ; Humans ; Ligands ; Medical sciences ; Methylcholanthrene - metabolism ; Methylcholanthrene - pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Organ Size - drug effects ; Pharmacology. Drug treatments ; Polychlorinated Biphenyls - metabolism ; Polychlorinated Biphenyls - pharmacology ; Receptors, Aryl Hydrocarbon - agonists ; Receptors, Aryl Hydrocarbon - genetics ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Transfection ; Tumors ; Uterus - anatomy & histology ; Uterus - drug effects</subject><ispartof>Cancer research (Chicago, Ill.), 2006-02, Vol.66 (4), p.2459-2467</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-e71c8f630d65f84b2acfdb9e9e083136f50f2f1a81e3cd3de2fce619ad8261cc3</citedby><cites>FETCH-LOGICAL-c415t-e71c8f630d65f84b2acfdb9e9e083136f50f2f1a81e3cd3de2fce619ad8261cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17605991$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16489053$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ABDELRAHIM, Maen</creatorcontrib><creatorcontrib>ARIAZI, Eric</creatorcontrib><creatorcontrib>JORDAN, V. Craig</creatorcontrib><creatorcontrib>SAFE, Stephen</creatorcontrib><creatorcontrib>KIM, Kyounghyun</creatorcontrib><creatorcontrib>KHAN, Shaheen</creatorcontrib><creatorcontrib>BARHOUMI, Rola</creatorcontrib><creatorcontrib>BURGHARDT, Robert</creatorcontrib><creatorcontrib>SHENGXI LIU</creatorcontrib><creatorcontrib>HILL, Denise</creatorcontrib><creatorcontrib>FINNELL, Richard</creatorcontrib><creatorcontrib>WLODARCZYK, Bogdan</creatorcontrib><title>3-methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor α</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>3-Methylcholanthrene (3MC) is an aryl hydrocarbon receptor (AhR) agonist, and it has been reported that 3MC induces estrogenic activity through AhR-estrogen receptor alpha (ER alpha) interactions. 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These results show that PCB and 3MC directly activate ER alpha-dependent transactivation and extend the number of ligands that activate both AhR and ER alpha.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Chromatin Immunoprecipitation</subject><subject>Cyclin D1 - biosynthesis</subject><subject>Cyclin D1 - genetics</subject><subject>Dimerization</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Female</subject><subject>Fluorescence Resonance Energy Transfer</subject><subject>Humans</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Methylcholanthrene - metabolism</subject><subject>Methylcholanthrene - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Organ Size - drug effects</subject><subject>Pharmacology. Drug treatments</subject><subject>Polychlorinated Biphenyls - metabolism</subject><subject>Polychlorinated Biphenyls - pharmacology</subject><subject>Receptors, Aryl Hydrocarbon - agonists</subject><subject>Receptors, Aryl Hydrocarbon - genetics</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Transfection</subject><subject>Tumors</subject><subject>Uterus - anatomy & histology</subject><subject>Uterus - drug effects</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1u2zAQhYmiQe2kPUILbdqdHI4o_mgZGG0TIEg2yZqgyaGlQhZdki7gY-UiOVNoxKizy2rA4TccvvcI-Qp0AcDVJaVU1byVzWJ5dVdTXjNgzQcyB85ULduWfyTz_8yMnKf0pxw5UP6JzEC0qqOczUnP6g3mfj_aPoxmyn3ECSszuSrkHmNl4n6s-r2LwZq4ClMV0eI2h3KzDtOQcqrcUHp53FfG5uGfyVhhyjGs8Q38_PSZnHkzJvxyrBfk8dfPh-V1fXv_-2Z5dVvbFniuUYJVXjDqBPeqXTXGerfqsEOqikLhOfWNB6MAmXXMYeMtCuiMU40Aa9kF-fH67jaGv7vyE70ZksWxiMOwS1pIIUEp9S4IkiopeVdA_graGFKK6PU2DptijAaqD1nog8_64LMuWWjK9SGLMvftuGC32qA7TR3NL8D3I2CSNaOPZrJDOnFSUN51wF4ATDmVcg</recordid><startdate>20060215</startdate><enddate>20060215</enddate><creator>ABDELRAHIM, Maen</creator><creator>ARIAZI, Eric</creator><creator>JORDAN, V. 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Craig ; SAFE, Stephen ; KIM, Kyounghyun ; KHAN, Shaheen ; BARHOUMI, Rola ; BURGHARDT, Robert ; SHENGXI LIU ; HILL, Denise ; FINNELL, Richard ; WLODARCZYK, Bogdan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-e71c8f630d65f84b2acfdb9e9e083136f50f2f1a81e3cd3de2fce619ad8261cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Chromatin Immunoprecipitation</topic><topic>Cyclin D1 - biosynthesis</topic><topic>Cyclin D1 - genetics</topic><topic>Dimerization</topic><topic>Estradiol - pharmacology</topic><topic>Estrogen Receptor alpha - genetics</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Female</topic><topic>Fluorescence Resonance Energy Transfer</topic><topic>Humans</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Methylcholanthrene - metabolism</topic><topic>Methylcholanthrene - pharmacology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Organ Size - drug effects</topic><topic>Pharmacology. 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Craig</creatorcontrib><creatorcontrib>SAFE, Stephen</creatorcontrib><creatorcontrib>KIM, Kyounghyun</creatorcontrib><creatorcontrib>KHAN, Shaheen</creatorcontrib><creatorcontrib>BARHOUMI, Rola</creatorcontrib><creatorcontrib>BURGHARDT, Robert</creatorcontrib><creatorcontrib>SHENGXI LIU</creatorcontrib><creatorcontrib>HILL, Denise</creatorcontrib><creatorcontrib>FINNELL, Richard</creatorcontrib><creatorcontrib>WLODARCZYK, Bogdan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ABDELRAHIM, Maen</au><au>ARIAZI, Eric</au><au>JORDAN, V. Craig</au><au>SAFE, Stephen</au><au>KIM, Kyounghyun</au><au>KHAN, Shaheen</au><au>BARHOUMI, Rola</au><au>BURGHARDT, Robert</au><au>SHENGXI LIU</au><au>HILL, Denise</au><au>FINNELL, Richard</au><au>WLODARCZYK, Bogdan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3-methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor α</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2006-02-15</date><risdate>2006</risdate><volume>66</volume><issue>4</issue><spage>2459</spage><epage>2467</epage><pages>2459-2467</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>3-Methylcholanthrene (3MC) is an aryl hydrocarbon receptor (AhR) agonist, and it has been reported that 3MC induces estrogenic activity through AhR-estrogen receptor alpha (ER alpha) interactions. In this study, we used 3MC and 3,3',4,4',5-pentachlorobiphenyl (PCB) as prototypical AhR ligands, and both compounds activated estrogen-responsive reporter genes/gene products (cathepsin D) in MCF-7 breast cancer cells. The estrogenic responses induced by these AhR ligands were inhibited by the antiestrogen ICI 182780 and by the transfection of a small inhibitory RNA for ER alpha but were not affected by the small inhibitory RNA for AhR. These results suggest that 3MC and PCB directly activate ER alpha, and this was confirmed in a competitive ER alpha binding assay and in a fluorescence resonance energy transfer experiment in which PCB and 3MC induced CFP-ER alpha/YFP-ER alpha interactions. In a chromatin immunoprecipitation assay, PCB and 3MC enhanced ER alpha (but not AhR) association with the estrogen-responsive region of the pS2 gene promoter. Moreover, in AhR knockout mice, 3MC increased uterine weights and induced expression of cyclin D1 mRNA levels. These results show that PCB and 3MC directly activate ER alpha-dependent transactivation and extend the number of ligands that activate both AhR and ER alpha.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16489053</pmid><doi>10.1158/0008-5472.CAN-05-3132</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 2006-02, Vol.66 (4), p.2459-2467 |
| issn | 0008-5472 1538-7445 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Animals Antineoplastic agents Binding, Competitive Biological and medical sciences Breast Neoplasms - genetics Breast Neoplasms - metabolism Cell Line, Tumor Chromatin Immunoprecipitation Cyclin D1 - biosynthesis Cyclin D1 - genetics Dimerization Estradiol - pharmacology Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Female Fluorescence Resonance Energy Transfer Humans Ligands Medical sciences Methylcholanthrene - metabolism Methylcholanthrene - pharmacology Mice Mice, Inbred C57BL Mice, Knockout Organ Size - drug effects Pharmacology. Drug treatments Polychlorinated Biphenyls - metabolism Polychlorinated Biphenyls - pharmacology Receptors, Aryl Hydrocarbon - agonists Receptors, Aryl Hydrocarbon - genetics RNA, Messenger - biosynthesis RNA, Messenger - genetics Transfection Tumors Uterus - anatomy & histology Uterus - drug effects |
| title | 3-methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor α |
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