Breast Cancer Research and Treatment

, Volume 73, Issue 1, pp 75–83 | Cite as

Effect of Selective Ablation of Proliferating Mammary Epithelial Cells on MNU Induced Rat Mammary Tumorigenesis

  • Lakshmi Sivaraman
  • Jason Gay
  • Susan G Hilsenbeck
  • H David Shine
  • Orla M Conneely
  • Daniel Medina
  • Bert W O'Malley


Proliferating cells within the terminal end buds of the virgin female rat mammary gland are the most susceptible to chemical carcinogen induced tumorigenesis. We hypothesized that selective ablation of proliferating cells in the mammary gland would reduce mammary tumor incidence upon carcinogen challenge. Selective ablation of proliferating cells was achieved by intraductal injections of Adv-RSV-tk and gancyclovir administration. Despite efficient viral transduction of the thymidine kinase protein and the apparent elimination of >90% of the prolif-erating cells, the rats exhibited a higher incidence of MNU induced mammary tumors arising with shorter latency as compared to control animals. Several possible explanations of the puzzling relationship between elimination of cycling cells and increased tumor incidence are discussed and alternative strategies for the prevention of breast cancer are proposed.

Adv-RSV-tk/GCV carcinogenesis mammary gland MNU proliferating cells 


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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Lakshmi Sivaraman
    • 1
  • Jason Gay
    • 1
  • Susan G Hilsenbeck
    • 2
  • H David Shine
    • 3
    • 4
    • 5
    • 6
  • Orla M Conneely
    • 1
  • Daniel Medina
    • 1
  • Bert W O'Malley
    • 1
  1. 1.Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA
  2. 2.Breast CenterBaylor College of MedicineHoustonUSA
  3. 3.Department of Molecular and Cellular BiologyUSA
  4. 4.Department of NeurosurgeryUSA
  5. 5.Division of NeuroscienceUSA
  6. 6.Center for Cell and Gene TherapyBaylor College of MedicineHoustonUSA

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