| Tamoxifen and ICI 182,780 increase Bcl-2 levels and inhibit growth of breast carcinoma cells by modulating PI3K/AKT, ERK and IGF-1R pathways independent of ERalpha. | |
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MedLine Citation:
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PMID: 19002577 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We recently showed that estrogen withdrawal from the ERalpha(+), high Bcl-2-expressing breast carcinoma cells (MCF-7B) reduced Bcl-2 protein levels while increasing cell-cell adhesion, and junction formation. Here we compared these cells with the ERalpha(+) and low Bcl-2-expressing MCF-7 cells and with the normal mammary epithelial cell line MCF-10-2A not expressing ERalpha or Bcl-2. All cell lines expressed normal HER2. Antiestrogen (Tamoxifen and ICI 182,780) treatment increased Bcl-2 levels in both MCF-7 and -7B cells and led to the formation of acinar structures. This treatment led to the dissociation of junctions and redistribution of junctional components to the cytoplasm in MCF-10-2A and -7 cells, while in MCF-7B cells junctional proteins redistributed to membranes. Antiestrogen treatment decreased PI3K/Akt activation and increased ERK activation regardless of ERalpha status. IGF-1R was inactivated in the antiestrogen-treated MCF-7 cells while it was activated in MCF-7B cells. Our data show that Tamoxifen and ICI 182,780 can induce growth inhibitory effects via the sustained activation/inactivation of signaling pathways that regulate cell survival, cell death and differentiation in the absence of ERalpha. Furthermore, Bcl-2 overexpression may alter the functional interactions among these pathways in response to antiestrogens, which also may provide a potential explanation for the observation that Bcl-2 overexpressing tumors have a better prognosis. |
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Authors:
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Le Lam; Xiuying Hu; Zackie Aktary; David W Andrews; Manijeh Pasdar |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-11 |
Journal Detail:
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Title: Breast cancer research and treatment Volume: 118 ISSN: 1573-7217 ISO Abbreviation: Breast Cancer Res. Treat. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-10 Completed Date: 2010-01-22 Revised Date: 2013-06-11 |
Medline Journal Info:
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Nlm Unique ID: 8111104 Medline TA: Breast Cancer Res Treat Country: Netherlands |
Other Details:
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Languages: eng Pagination: 605-21 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, University of Alberta, 6-24 Medical Sciences Building, Edmonton, AB, Canada, T6G 2H7. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Breast Neoplasms / metabolism* Cell Adhesion / drug effects Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Connexins / drug effects Estradiol / analogs & derivatives*, pharmacology Estrogen Receptor alpha / drug effects, metabolism Extracellular Signal-Regulated MAP Kinases / drug effects, metabolism Female Fluorescent Antibody Technique Humans Phosphatidylinositol 3-Kinases / drug effects, metabolism Proto-Oncogene Proteins c-akt / drug effects, metabolism Proto-Oncogene Proteins c-bcl-2 / drug effects*, metabolism Receptor, IGF Type 1 / drug effects, metabolism Selective Estrogen Receptor Modulators / pharmacology* Signal Transduction / drug effects* Tamoxifen / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Connexins; 0/Estrogen Receptor alpha; 0/Proto-Oncogene Proteins c-bcl-2; 0/Selective Estrogen Receptor Modulators; 10540-29-1/Tamoxifen; 22X328QOC4/fulvestrant; 50-28-2/Estradiol; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Receptor, IGF Type 1; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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