The Bik BH3-Only Protein Is Induced in Estrogen-Starved and Antiestrogen-Exposed Breast Cancer Cells and Provokes Apoptosis
Evidence has been accumulating that some estrogen-dependent human breast cancers require estrogen for not only proliferation but also survival. To obtain insights into the molecular mechanisms of apoptosis of breast cancer cells subjected to estrogen starvation or exposed to antiestrogens, we charac...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2004-02, Vol.101 (8), p.2351-2356 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Hur, Jingyung Chesnes, Jessica Coser, Kathryn R. Lee, Roseanna S. Geck, Peter Isselbacher, Kurt J. Shioda, Toshi |
| description | Evidence has been accumulating that some estrogen-dependent human breast cancers require estrogen for not only proliferation but also survival. To obtain insights into the molecular mechanisms of apoptosis of breast cancer cells subjected to estrogen starvation or exposed to antiestrogens, we characterized changes in the gene expression profile of MCF-7/BUS human breast cancer cells and revealed a strong induction of Bik, a member of the BH3-only proapoptotic proteins. The Bik mRNA transcript and protein were strongly induced by estrogen starvation or exposure to fulvestrant, a pure antiestrogen that competes with the natural estrogens for binding to the estrogen receptors. This Bik induction preceded apoptotic cell death, which was blocked by zVAD-fmk, a pancaspase inhibitor. Amounts of the Bcl-2-related proteins, such as Bcl-2, Bcl- XL, or Bax, showed only marginal changes in the presence or absence of estrogens or antiestrogens. Suppression of Bik expression by using the small interfering RNA effectively blocked the fulvestrant-induced breast cancer cell apoptosis. These results indicate that Bik is induced in MCF-7/BUS cells in the absence of estrogen signaling and plays a critical role in the antiestrogen-provoked breast cancer cell apoptosis. |
| doi_str_mv | 10.1073/pnas.0307337101 |
| format | Article |
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To obtain insights into the molecular mechanisms of apoptosis of breast cancer cells subjected to estrogen starvation or exposed to antiestrogens, we characterized changes in the gene expression profile of MCF-7/BUS human breast cancer cells and revealed a strong induction of Bik, a member of the BH3-only proapoptotic proteins. The Bik mRNA transcript and protein were strongly induced by estrogen starvation or exposure to fulvestrant, a pure antiestrogen that competes with the natural estrogens for binding to the estrogen receptors. This Bik induction preceded apoptotic cell death, which was blocked by zVAD-fmk, a pancaspase inhibitor. Amounts of the Bcl-2-related proteins, such as Bcl-2, Bcl- XL, or Bax, showed only marginal changes in the presence or absence of estrogens or antiestrogens. Suppression of Bik expression by using the small interfering RNA effectively blocked the fulvestrant-induced breast cancer cell apoptosis. These results indicate that Bik is induced in MCF-7/BUS cells in the absence of estrogen signaling and plays a critical role in the antiestrogen-provoked breast cancer cell apoptosis.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0307337101</identifier><identifier>PMID: 14983013</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Apoptosis ; Apoptosis - drug effects ; Apoptosis Regulatory Proteins ; Base Sequence ; Biological Sciences ; Breast cancer ; Breast Neoplasms ; Cell culture techniques ; Cell Line, Tumor ; Cell lines ; Cellular biology ; Cultured cells ; DNA Primers ; Estradiol - pharmacology ; Estrogen receptor modulators ; Estrogen Receptor Modulators - pharmacology ; Estrogens ; Estrogens - pharmacology ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Kinetics ; Membrane Proteins - genetics ; Messenger RNA ; Proteins ; RNA, Small Interfering - genetics ; Small interfering RNA ; Starvation ; Transcription, Genetic - drug effects ; Transfection</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2004-02, Vol.101 (8), p.2351-2356</ispartof><rights>Copyright 1993/2004 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 24, 2004</rights><rights>Copyright © 2004, The National Academy of Sciences 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-7e5a2ac0d746f89802ba9ced4907dd66c2bd788331533e450a7056fce71669193</citedby><cites>FETCH-LOGICAL-c588t-7e5a2ac0d746f89802ba9ced4907dd66c2bd788331533e450a7056fce71669193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/101/8.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3371295$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3371295$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,729,782,786,805,887,27931,27932,53798,53800,58024,58257</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14983013$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hur, Jingyung</creatorcontrib><creatorcontrib>Chesnes, Jessica</creatorcontrib><creatorcontrib>Coser, Kathryn R.</creatorcontrib><creatorcontrib>Lee, Roseanna S.</creatorcontrib><creatorcontrib>Geck, Peter</creatorcontrib><creatorcontrib>Isselbacher, Kurt J.</creatorcontrib><creatorcontrib>Shioda, Toshi</creatorcontrib><title>The Bik BH3-Only Protein Is Induced in Estrogen-Starved and Antiestrogen-Exposed Breast Cancer Cells and Provokes Apoptosis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Evidence has been accumulating that some estrogen-dependent human breast cancers require estrogen for not only proliferation but also survival. To obtain insights into the molecular mechanisms of apoptosis of breast cancer cells subjected to estrogen starvation or exposed to antiestrogens, we characterized changes in the gene expression profile of MCF-7/BUS human breast cancer cells and revealed a strong induction of Bik, a member of the BH3-only proapoptotic proteins. The Bik mRNA transcript and protein were strongly induced by estrogen starvation or exposure to fulvestrant, a pure antiestrogen that competes with the natural estrogens for binding to the estrogen receptors. This Bik induction preceded apoptotic cell death, which was blocked by zVAD-fmk, a pancaspase inhibitor. Amounts of the Bcl-2-related proteins, such as Bcl-2, Bcl- XL, or Bax, showed only marginal changes in the presence or absence of estrogens or antiestrogens. Suppression of Bik expression by using the small interfering RNA effectively blocked the fulvestrant-induced breast cancer cell apoptosis. 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To obtain insights into the molecular mechanisms of apoptosis of breast cancer cells subjected to estrogen starvation or exposed to antiestrogens, we characterized changes in the gene expression profile of MCF-7/BUS human breast cancer cells and revealed a strong induction of Bik, a member of the BH3-only proapoptotic proteins. The Bik mRNA transcript and protein were strongly induced by estrogen starvation or exposure to fulvestrant, a pure antiestrogen that competes with the natural estrogens for binding to the estrogen receptors. This Bik induction preceded apoptotic cell death, which was blocked by zVAD-fmk, a pancaspase inhibitor. Amounts of the Bcl-2-related proteins, such as Bcl-2, Bcl- XL, or Bax, showed only marginal changes in the presence or absence of estrogens or antiestrogens. Suppression of Bik expression by using the small interfering RNA effectively blocked the fulvestrant-induced breast cancer cell apoptosis. These results indicate that Bik is induced in MCF-7/BUS cells in the absence of estrogen signaling and plays a critical role in the antiestrogen-provoked breast cancer cell apoptosis.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>14983013</pmid><doi>10.1073/pnas.0307337101</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Apoptosis - drug effects Apoptosis Regulatory Proteins Base Sequence Biological Sciences Breast cancer Breast Neoplasms Cell culture techniques Cell Line, Tumor Cell lines Cellular biology Cultured cells DNA Primers Estradiol - pharmacology Estrogen receptor modulators Estrogen Receptor Modulators - pharmacology Estrogens Estrogens - pharmacology Female Gene Expression Regulation, Neoplastic - drug effects Humans Kinetics Membrane Proteins - genetics Messenger RNA Proteins RNA, Small Interfering - genetics Small interfering RNA Starvation Transcription, Genetic - drug effects Transfection |
| title | The Bik BH3-Only Protein Is Induced in Estrogen-Starved and Antiestrogen-Exposed Breast Cancer Cells and Provokes Apoptosis |
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