| Reversal of an antiestrogen-mediated cell cycle arrest of MCF-7 cells by viral tumor antigens requires the retinoblastoma protein-binding domain. | |
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MedLine Citation:
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PMID: 11032025 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Proliferation of MCF-7 cells is estrogen dependent and antiestrogen sensitive. In the absence of estrogens or presence of antiestrogens MCF-7 cells arrest in the G1 phase of the cell cycle, and this arrest is associated with an accumulation of the active, hypophosphorylated form of the retinoblastoma protein (pRb). Because active pRb negatively regulates passage from G1 to S phase, this suggests that pRb is a crucial target of estrogen action, and that its inactivation might lead to antiestrogen resistance. We tested this hypothesis by expressing viral tumor antigens (T antigens), which bind and inactivate pRb, in MCF-7 cells, and determining the effects on cell proliferation in the presence of antiestrogens. The results of these experiments demonstrate that T antigen expression confers antiestrogen resistance to MCF-7 cells. Using a panel of mutant T antigens, we further demonstrate that the pRb-binding, but not the p53 binding domain is required to confer antiestrogen resistance. Thus, pRb is an important target of estrogen action, and its inactivation can contribute to the development of antiestrogen resistance. |
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Authors:
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H Varma; S E Conrad |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Oncogene Volume: 19 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2000 Sep |
Date Detail:
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Created Date: 2000-11-13 Completed Date: 2000-11-13 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 4746-53 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Michigan State University, East Lansing 48824-1101, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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pathology* Antigens, Polyomavirus Transforming / metabolism, physiology* Antineoplastic Agents, Hormonal / pharmacology* Breast Neoplasms / pathology* Cyclin D1 / physiology Drug Resistance, Neoplasm Estradiol / analogs & derivatives*, pharmacology Estrogen Receptor Modulators / pharmacology* Estrogens* Female G1 Phase / drug effects Humans Neoplasm Proteins / antagonists & inhibitors, physiology* Neoplasms, Hormone-Dependent / pathology* Protein Structure, Tertiary Recombinant Fusion Proteins / physiology Retinoblastoma Protein / antagonists & inhibitors, physiology* Tamoxifen / analogs & derivatives*, pharmacology Transfection Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA76647/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Polyomavirus Transforming; 0/Antineoplastic Agents, Hormonal; 0/Estrogen Receptor Modulators; 0/Estrogens; 0/Neoplasm Proteins; 0/Recombinant Fusion Proteins; 0/Retinoblastoma Protein; 10540-29-1/Tamoxifen; 129453-61-8/fulvestrant; 136601-57-5/Cyclin D1; 50-28-2/Estradiol; 68392-35-8/4-hydroxytamoxifen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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