Breast Cancer Research and Treatment

, Volume 77, Issue 3, pp 253–264

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

  • Konstantin Christov
  • Amy Ikui
  • Anne Shilkaitis
  • Albert Green
  • Ruisheng Yao
  • Ming You
  • Clinton Grubbs
  • Vernon Steele
  • Ronald Lubet
  • I. Bernard Weinstein
Article

DOI: 10.1023/A:1021804121171

Cite this article as:
Christov, K., Ikui, A., Shilkaitis, A. et al. Breast Cancer Res Treat (2003) 77: 253. doi:10.1023/A:1021804121171
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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).

apoptosis cyclin D1 mammary tumors proliferation tamoxifen 

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Konstantin Christov
    • 1
  • Amy Ikui
    • 2
  • Anne Shilkaitis
    • 1
  • Albert Green
    • 1
  • Ruisheng Yao
    • 3
  • Ming You
    • 3
  • Clinton Grubbs
    • 4
  • Vernon Steele
    • 5
  • Ronald Lubet
    • 5
  • I. Bernard Weinstein
    • 2
  1. 1.Department of Surgical OncologyUniversity of IllinoisChicagoUSA
  2. 2.Herbert Irving Comprehensive Cancer CenterColumbia UniversityNew YorkUSA
  3. 3.Department of Human GeneticsOhio State UniversityColumbusUSA
  4. 4.Prevention CenterUniversity of AlabamaBirminghamUSA
  5. 5.Division of Cancer PreventionNational Cancer InstituteBethesdaUSA

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