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Article: An Activator Protein 1-Like Motif Mediates 17β-Estradiol Repression of Gonadotropin-Releasing Hormone Receptor Promoter via an Estrogen Receptor α-Dependent Mechanism in Ovarian and Breast Cancer Cells

TitleAn Activator Protein 1-Like Motif Mediates 17β-Estradiol Repression of Gonadotropin-Releasing Hormone Receptor Promoter via an Estrogen Receptor α-Dependent Mechanism in Ovarian and Breast Cancer Cells
Authors
Issue Date2003
PublisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/
Citation
Molecular Endocrinology, 2003, v. 17 n. 12, p. 2613-2629 How to Cite?
AbstractAlthough it is recognized that estrogen is one of the most important regulators of GnRH receptor (GnRHR) gene expression, the mechanism underlying the regulation at the transcriptional level is unknown. In the present study, we demonstrated that 17β-estradiol (E2) repressed human GnRHR promoter via an activator protein 1-like motif and estrogen receptor-α, of which the DNA-binding domain and the ligand-binding domain were indispensable for the repression. Interestingly, the same cis-acting motif was also found to be important for both the basal activity and phorbol 12-myristate 13-acetate responsiveness of the GnRHR promoter. EMSAs indicated that multiple transcription factors including c-Jun and c-Fos bound to the activator protein 1-like site and that their DNA binding activity was not significantly affected by E2 treatment. In addition, we demonstrated that the E2 repression could be antagonized by phorbol 12-myristate 13-acetate, which stimulated c-Jun phosphorylation on serine 63, a process that is a prerequisite for recruitment of the transcriptional coactivator cAMP response element binding protein (CREB)-binding protein (CBP). Concomitantly, we found that overexpression of CBP could reverse the suppression in a dose-dependent manner. Taken together, our data indicate that E2-activated estrogen receptor-α represses human GnRHR gene transcription via an indirect mechanism involving CBP and possibly other transcriptional regulators.
Persistent Identifierhttp://hdl.handle.net/10722/178837
ISSN
2015 Impact Factor: 3.432
2015 SCImago Journal Rankings: 2.195
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheng, CKen_US
dc.contributor.authorChow, BKCen_US
dc.contributor.authorLeung, PCKen_US
dc.date.accessioned2012-12-19T09:50:02Z-
dc.date.available2012-12-19T09:50:02Z-
dc.date.issued2003en_US
dc.identifier.citationMolecular Endocrinology, 2003, v. 17 n. 12, p. 2613-2629en_US
dc.identifier.issn0888-8809en_US
dc.identifier.urihttp://hdl.handle.net/10722/178837-
dc.description.abstractAlthough it is recognized that estrogen is one of the most important regulators of GnRH receptor (GnRHR) gene expression, the mechanism underlying the regulation at the transcriptional level is unknown. In the present study, we demonstrated that 17β-estradiol (E2) repressed human GnRHR promoter via an activator protein 1-like motif and estrogen receptor-α, of which the DNA-binding domain and the ligand-binding domain were indispensable for the repression. Interestingly, the same cis-acting motif was also found to be important for both the basal activity and phorbol 12-myristate 13-acetate responsiveness of the GnRHR promoter. EMSAs indicated that multiple transcription factors including c-Jun and c-Fos bound to the activator protein 1-like site and that their DNA binding activity was not significantly affected by E2 treatment. In addition, we demonstrated that the E2 repression could be antagonized by phorbol 12-myristate 13-acetate, which stimulated c-Jun phosphorylation on serine 63, a process that is a prerequisite for recruitment of the transcriptional coactivator cAMP response element binding protein (CREB)-binding protein (CBP). Concomitantly, we found that overexpression of CBP could reverse the suppression in a dose-dependent manner. Taken together, our data indicate that E2-activated estrogen receptor-α represses human GnRHR gene transcription via an indirect mechanism involving CBP and possibly other transcriptional regulators.en_US
dc.languageengen_US
dc.publisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/en_US
dc.relation.ispartofMolecular Endocrinologyen_US
dc.rightsMolecular Endocrinology. Copyright © The Endocrine Society.-
dc.subject.meshBase Sequenceen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshBreast Neoplasmsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshDna, Neoplasm - Chemistry - Metabolismen_US
dc.subject.meshEstradiol - Pharmacologyen_US
dc.subject.meshEstrogen Receptor Alphaen_US
dc.subject.meshFemaleen_US
dc.subject.meshForskolin - Pharmacologyen_US
dc.subject.meshHumansen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshOvarian Neoplasmsen_US
dc.subject.meshPromoter Regions, Genetic - Drug Effects - Geneticsen_US
dc.subject.meshReceptors, Estrogen - Physiologyen_US
dc.subject.meshReceptors, Lhrh - Geneticsen_US
dc.subject.meshTetradecanoylphorbol Acetate - Pharmacologyen_US
dc.subject.meshTranscription Factor Ap-1 - Metabolismen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.titleAn Activator Protein 1-Like Motif Mediates 17β-Estradiol Repression of Gonadotropin-Releasing Hormone Receptor Promoter via an Estrogen Receptor α-Dependent Mechanism in Ovarian and Breast Cancer Cellsen_US
dc.typeArticleen_US
dc.identifier.emailChow, BKC: bkcc@hku.hken_US
dc.identifier.authorityChow, BKC=rp00681en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1210/me.2003-0217en_US
dc.identifier.pmid12947046-
dc.identifier.scopuseid_2-s2.0-0346849701en_US
dc.identifier.hkuros91135-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0346849701&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume17en_US
dc.identifier.issue12en_US
dc.identifier.spage2613en_US
dc.identifier.epage2629en_US
dc.identifier.isiWOS:000187072900019-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridCheng, CK=7404797040en_US
dc.identifier.scopusauthoridChow, BKC=7102826193en_US
dc.identifier.scopusauthoridLeung, PCK=55419381000en_US

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