| Estrogen receptor regulates E2F1 expression to mediate tamoxifen resistance. | |
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MedLine Citation:
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PMID: 20215421 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Antiestrogen resistance often develops with prolonged exposure to hormone therapies, including tamoxifen, and is a major problem in the treatment of breast cancer. Understanding the mechanisms involved in the development of antiestrogen resistance is an important step in the development of new targeted therapies. Two forms of antiestrogen resistance exist: de novo resistance and acquired resistance. To mimic acquired resistance, we have established a tamoxifen-resistant breast cancer cell line (MCF-7TamR) by treating parental MCF-7 cells with tamoxifen over a period of 6 months to select for cells with the resistant phenotype. Characterization of the MCF-7TamR cells under normal, hormone-deprived, and tamoxifen-treated conditions suggests that these cells continue to grow in the presence of tamoxifen. Additionally, a greater percentage of resistant cells enter the S phase under tamoxifen conditions, compared with parental MCF-7 cells. Consistent with these growth results, molecular analysis indicates that tamoxifen-resistant cells express higher levels of cyclin E1, cdk2, ACTR, and E2F1. Faslodex or ICI 182, 780 (ICI)-mediated degradation of estrogen receptor (ER) reduced the proliferation of these cells, as well as the level of E2F1 expression in tamoxifen-resistant cells, suggesting that tamoxifen resistance and E2F1 expression are in part dependent on ER. We further showed that tamoxifen enhances the ERalpha/Sp-1 interaction and promotes the recruitment of ERalpha and Sp-1 to the proximal promoter of E2F1 in resistant cells. Collectively, our findings suggest that tamoxifen resistance is a result of increased ERalpha/Sp-1 interaction, which enhances the expression of E2F1 to promote tamoxifen resistance. |
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Authors:
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Maggie C Louie; Ashley McClellan; Christina Siewit; Lauren Kawabata |
Publication Detail:
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Type: Journal Article Date: 2010-03-09 |
Journal Detail:
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Title: Molecular cancer research : MCR Volume: 8 ISSN: 1557-3125 ISO Abbreviation: Mol. Cancer Res. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-18 Completed Date: 2010-07-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101150042 Medline TA: Mol Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 343-52 Citation Subset: IM |
Affiliation:
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Department of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA 94901, USA. maggie.louie@dominican.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Breast Neoplasms
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drug therapy*,
genetics*,
metabolism Cell Cycle Proteins / drug effects, genetics, metabolism Cell Line, Tumor Drug Resistance, Neoplasm / genetics* E2F1 Transcription Factor / drug effects, genetics*, metabolism Estradiol / analogs & derivatives, pharmacology Estrogen Receptor alpha / drug effects, genetics*, metabolism Gene Expression Regulation, Neoplastic / genetics* Genes, cdc / drug effects, physiology Humans Immunoglobulins / drug effects, metabolism Promoter Regions, Genetic / drug effects, genetics S Phase / drug effects, physiology Selective Estrogen Receptor Modulators / pharmacology Tamoxifen / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/Estrogen Receptor alpha; 0/Immunoglobulins; 0/SP1 antigen; 0/Selective Estrogen Receptor Modulators; 10540-29-1/Tamoxifen; 129453-61-8/fulvestrant; 50-28-2/Estradiol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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