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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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-02, Vol.101 (8), p.2351-2356
Main Authors: Hur, Jingyung, Chesnes, Jessica, Coser, Kathryn R., Lee, Roseanna S., Geck, Peter, Isselbacher, Kurt J., Shioda, Toshi
Format: Article
Language:English
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0307337101