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Cell Proliferation, Apoptosis, and Expression of Cyclin D1 and Cyclin E as Potential Biomarkers in Tamoxifen-Treated Mammary Tumors

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Abstract

Tamoxifen has been widely used for treatment, and more recently, for the prevention of breast cancer. Since breast carcinomas are composed of heterogeneous populations of estrogen receptor-positive (ER+) cells, we hypothesized that tamoxifen may suppress tumor growth by differentially affecting cell proliferation and apoptosis. ER+ mammary tumors were induced in Sprague–Dawley rats by N-methyl-N-nitrosourea (MNU) and when they became palpable, the animals were treated for 5, 10, or 20 days with tamoxifen, 1.0 mg/kg body weight. Tamoxifen induced a time-dependent decrease in proliferating (BrdU-labeled) cells, arrested the cells in G1/0 phase, and differentially decreased the cyclin E and cyclin D1 expression at mRNA and protein levels. In the same tumors, apoptotic cells increased during the first 10 days of treatment, but their number remained unchanged with extension of the treatment to 20 days. Thus, we provide data that tamoxifen may differentially affect cell proliferation and apoptosis in mammary tumors and that the expression levels of cyclin D1 and cyclin E might also be considered potential intermediate biomarkers of response of mammary tumors to tamoxifen and possibly to other selective estrogen receptor modulators (SERMs).

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Authors and Affiliations

  1. Department of Surgical Oncology, University of Illinois, Chicago, IL, USA

    Konstantin Christov, Anne Shilkaitis & Albert Green

  2. Herbert Irving Comprehensive Cancer Center, Columbia University, New York, USA

    Amy Ikui & I. Bernard Weinstein

  3. Department of Human Genetics, Ohio State University, Columbus, OH, USA

    Ruisheng Yao & Ming You

  4. Prevention Center, University of Alabama, Birmingham, AL, USA

    Clinton Grubbs

  5. Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA

    Vernon Steele & Ronald Lubet

Authors
  1. Konstantin Christov
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  2. Amy Ikui
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  3. Anne Shilkaitis
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  4. Albert Green
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  5. Ruisheng Yao
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  6. Ming You
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  7. Clinton Grubbs
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  8. Vernon Steele
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  9. Ronald Lubet
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  10. I. Bernard Weinstein
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Christov, K., Ikui, A., Shilkaitis, A. et al. Cell Proliferation, Apoptosis, and Expression of Cyclin D1 and Cyclin E as Potential Biomarkers in Tamoxifen-Treated Mammary Tumors. Breast Cancer Res Treat 77, 253–264 (2003). https://doi.org/10.1023/A:1021804121171

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