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Non-classical Genomic Estrogen Receptor (ER)/specificity Protein and ER/activating Protein-1 Signaling Pathways

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Date 2008 Sep 6
PMID 18772268
Citations 148
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Abstract

17beta-estradiol binds to the estrogen receptor (ER) to activate gene expression or repression and this involves both genomic (nuclear) and non-genomic (extranuclear) pathways. Genomic pathways include the classical interactions of ligand-bound ER dimers with estrogen-responsive elements in target gene promoters. ER-dependent activation of gene expression also involves DNA-bound ER that subsequently interacts with other DNA-bound transcriptions factors and direct ER-transcription factor (protein-protein) interactions where ER does not bind promoter DNA. Ligand-induced activation of ER/specificity protein (Sp) and ER/activating protein-1 [(AP-1); consisting of jun/fos] complexes are important pathways for modulating expression of a large number of genes. This review summarizes some of the characteristics of ER/Sp- and ER/AP-1-mediated transactivation, which are dependent on ligand structure, cell context, ER-subtype (ERalpha and ERbeta), and Sp protein (SP1, SP3, and SP4) and demonstrates that this non-classical genomic pathway is also functional in vivo.

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References
1.
Glidewell-Kenney C, Hurley L, Pfaff L, Weiss J, Levine J, Jameson J . Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis. Proc Natl Acad Sci U S A. 2007; 104(19):8173-7. PMC: 1876590. DOI: 10.1073/pnas.0611514104. View

2.
Fleming J, Spencer T, Safe S, Bazer F . Estrogen regulates transcription of the ovine oxytocin receptor gene through GC-rich SP1 promoter elements. Endocrinology. 2005; 147(2):899-911. DOI: 10.1210/en.2005-1120. View

3.
Fujimoto N, Honda H, Kitamura S . Effects of environmental estrogenic chemicals on AP1 mediated transcription with estrogen receptors alpha and beta. J Steroid Biochem Mol Biol. 2004; 88(1):53-9. DOI: 10.1016/j.jsbmb.2003.10.006. View

4.
Xie W, Duan R, Chen I, Samudio I, Safe S . Transcriptional activation of thymidylate synthase by 17beta-estradiol in MCF-7 human breast cancer cells. Endocrinology. 2000; 141(7):2439-49. DOI: 10.1210/endo.141.7.7538. View

5.
Qin C, Singh P, Safe S . Transcriptional activation of insulin-like growth factor-binding protein-4 by 17beta-estradiol in MCF-7 cells: role of estrogen receptor-Sp1 complexes. Endocrinology. 1999; 140(6):2501-8. DOI: 10.1210/endo.140.6.6751. View