| pS2 Gene expression in HepG2 cells: complex regulation through crosstalk between the estrogen receptor alpha, an estrogen-responsive element, and the activator protein 1 response element. | |
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MedLine Citation:
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PMID: 12021387 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The pS2 promoter is complex with binding sites for a number of protein factors that may participate in modulating its activity. The pS2 gene was transcriptionally activated by estrogens in HepG2 cells transformed (HepER3) to express the estrogen receptor alpha (ERalpha). The phorbol ester phorbol 12-myristate 13-acetate (PMA) stimulated pS2 expression in both HepER3 and the parental, non-ER-expressing HepG2 cells, although its activity was substantially less in HepG2 cells. The use of selective protein kinase inhibitors suggested that the MAPK pathway contributes substantially to estrogen stimulation of the pS2 promoter. The activator protein 1 (AP1) site at -332 to -338 in the pS2 promoter had a dominant role in the response to both estrogens and PMA, although the estrogen response element at -393 to -405 was essential to mediate the response to estrogen. The potentiation of pS2 promoter activity by the AP1 motif in response to estrogen was dependent on the ligand binding domain of ERalpha. Furthermore, the presence of an intact AP1 element in the pS2 promoter sustained suppression of pS2 promoter activity by an LXXLL peptide. In summary, the data suggest that the effect of estrogen is mediated through a cross-talk between the estrogen-responsive element and the AP1 response element and that ERalpha plays a crucial role in mediating the effect of both estrogen and PMA. |
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Authors:
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Tomas Barkhem; Lars-Arne Haldosén; Jan-Ake Gustafsson; Stefan Nilsson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular pharmacology Volume: 61 ISSN: 0026-895X ISO Abbreviation: Mol. Pharmacol. Publication Date: 2002 Jun |
Date Detail:
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Created Date: 2002-05-21 Completed Date: 2002-06-17 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 1273-83 Citation Subset: IM |
Affiliation:
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Karo Bio AB, Huddinge, Sweden. tomas.barkhem@karobio.se |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Motifs
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physiology Binding Sites Enzyme Inhibitors / pharmacology Estrogen Receptor alpha Gene Expression Regulation* / drug effects Humans Promoter Regions, Genetic / physiology Protein Biosynthesis* Protein Kinase Inhibitors Proteins / genetics Receptor Cross-Talk / physiology* Receptors, Cell Surface / biosynthesis, genetics Receptors, Estrogen / metabolism* Regulatory Sequences, Nucleic Acid / physiology* Repressor Proteins / metabolism Transcription Factor AP-1 / metabolism* Tumor Cells, Cultured Tumor Suppressor Proteins |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Estrogen Receptor alpha; 0/Protein Kinase Inhibitors; 0/Proteins; 0/Receptors, Cell Surface; 0/Receptors, Estrogen; 0/Repressor Proteins; 0/TFF1 protein, human; 0/Transcription Factor AP-1; 0/Tumor Suppressor Proteins; 0/sex hormone-binding globulin receptor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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