| Wild-type BRCA1, but not mutated BRCA1, regulates the expression of the nuclear form of beta-catenin. | |
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MedLine Citation:
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PMID: 20215423 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BRCA1 is an essential caretaker protein in the surveillance of DNA damage, is mutated in approximately 50% of all hereditary breast cancer cases, and its expression is frequently decreased in sporadic breast cancer. beta-Catenin is a multifunctional protein that forms adhesion complex with E-cadherins, alpha-catenin, and actin, and plays a central role in Wnt signaling through its nuclear translocation and activation of beta-catenin-responsive genes. Although significant progress has been made in understanding the Wnt/beta-catenin and BRCA1 signaling cascades, it is not known whether there is a link between beta-catenin and BRCA1. We observed that the expression of the active nuclear form of beta-catenin (also known as ABC, Ser37/Thr41-nonphosphorylated beta-catenin, dephosphorylated beta-catenin) was lower or absent in the nucleus in most BRCA1 familial breast cancer tissues (17 cases) compared with sporadic breast cancer (14 samples) and normal breast tissues. Wild-type-BRCA1, but not mutated BRCA1, interacted with beta-catenin and increased the levels of beta-catenin protein expression in vitro. Furthermore, H(2)O(2) induced the interaction of the nuclear form of beta-catenin with BRCA1. The active form of beta-catenin protein was downregulated upon exposure to H(2)O(2) in the nucleus of BRCA1-deficient HCC1937 breast cancer cells, whereas reconstitution of WT-BRCA1 in HCC1937 cells inhibited this downregulation. This study provides evidence of a novel interaction between BRCA1 and beta-catenin, and that loss of BRCA1 leads to impaired expression of the nuclear form of beta-catenin, which may contribute to the pathogenesis of breast cancer. |
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Authors:
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Huchun Li; Masayuki Sekine; Nadine Tung; Hava Karsenty Avraham |
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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; Research Support, U.S. Gov't, Non-P.H.S. 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: 2011-09-26 |
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: 407-20 Citation Subset: IM |
Affiliation:
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Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 99 Brookline Avenue, RN-330C, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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BRCA1 Protein
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genetics*,
metabolism Breast Neoplasms / genetics*, metabolism Carcinoma / genetics*, metabolism Cell Line, Tumor Cell Nucleus / genetics, metabolism Cell Transformation, Neoplastic / genetics, metabolism Down-Regulation / drug effects, genetics Female Gene Expression Regulation, Neoplastic / genetics* Humans Hydrogen Peroxide / pharmacology Mutation / genetics Oxidants / pharmacology Oxidative Stress / drug effects, genetics Signal Transduction / genetics beta Catenin / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA 096805/CA/NCI NIH HHS; CA135226/CA/NCI NIH HHS; R21 CA135226-01A1/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/BRCA1 Protein; 0/BRCA1 protein, human; 0/Oxidants; 0/beta Catenin; 7722-84-1/Hydrogen Peroxide |
| Comments/Corrections | |
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