| Resveratrol, through NF-Y/p53/Sin3/HDAC1 complex phosphorylation, inhibits estrogen receptor alpha gene expression via p38MAPK/CK2 signaling in human breast cancer cells. | |
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MedLine Citation:
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PMID: 21737614 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Agents to counteract acquired resistance to hormonal therapy for breast cancer would substantially enhance the long-term benefits of hormonal therapy. In the present study, we demonstrate how resveratrol (Res) inhibits human breast cancer cell proliferation, including MCF-7 tamoxifen-resistant cells (IC(50) values for viability were in the 30-45 μM range). We show that Res, through p38(MAPK) phosphorylation, causes induction of p53, which recruits at the estrogen receptor α (ERα) proximal promoter, leading to an inhibition of ERα expression in terms of mRNA and protein content. These events appear specifically p53 dependent, since they are drastically abrogated with p53-targeting siRNA. Coimmunoprecipitation assay showed specific interaction between p53, the Sin3A corepressor, and histone deacetylase 1 (HDAC1), which was phosphorylated. The enhancement of the tripartite complex p53/Sin3A/HDAC1, together with NF-Y on Res treatment, was confirmed by chromatin immunoprecipitation analyses, with a concomitant release of Sp1 and RNA polymerase II, thereby inhibiting the cell transcriptional machinery. The persistence of such effects in MCF-7 tamoxifen-resistant cells at a higher extent than parental MCF-7 cells addresses how Res may be considered a useful pharmacological tool to be exploited in the adjuvant settings for treatment of breast cancer developing hormonal resistance. |
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Authors:
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Francesca De Amicis; Francesca Giordano; Adele Vivacqua; Michele Pellegrino; Maria Luisa Panno; Donatella Tramontano; Suzanne A W Fuqua; Sebastiano Andò |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-07-07 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 25 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-03 Completed Date: 2011-12-07 Revised Date: 2013-02-08 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 3695-707 Citation Subset: IM |
Affiliation:
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Centro Sanitario, Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende (CS) 87030, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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pharmacology Breast Neoplasms / metabolism* CCAAT-Binding Factor / genetics, metabolism* Casein Kinase II / genetics, metabolism Cell Line, Tumor Estrogen Receptor alpha / genetics, metabolism Female Gene Expression Regulation, Neoplastic / drug effects Histone Deacetylase 1 / genetics, metabolism* Humans Sin3 Histone Deacetylase and Corepressor Complex / genetics, metabolism* Stilbenes / pharmacology* Tumor Suppressor Protein p53 / genetics, metabolism* p38 Mitogen-Activated Protein Kinases / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA072038-15/CA/NCI NIH HHS; R01 CA72038/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/CCAAT-Binding Factor; 0/Estrogen Receptor alpha; 0/Stilbenes; 0/Tumor Suppressor Protein p53; 501-36-0/resveratrol; EC 2.7.11.1/Casein Kinase II; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.5.1.98/HDAC1 protein, human; EC 3.5.1.98/Histone Deacetylase 1; EC 3.5.1.98/Sin3 Histone Deacetylase and Corepressor Complex |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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