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Physiologic estrogen receptor alpha signaling in non-tumorigenic human mammary epithelial cells

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Summary

Currently, a number of breast cancer cell lines exist that serve as models for both estrogen receptor alpha (ERα) positive and ERα negative disease. Models are also available for pre-neoplastic breast epithelial cells that do not express ERα; however, there are no ideal systems for studying pre-neoplastic cells that are ERα positive. This has been largely due to the inability to establish an estrogen growth stimulated, non-tumorigenic breast epithelial cell line, as most human breast epithelial cells engineered to overexpress ERα have been found to be growth inhibited by estrogens. We have developed independently derived clones from the non-cancerous MCF-10A human breast cell line that express ERα and are growth stimulated by 17-beta-estradiol (E2) in the absence of epidermal growth factor (EGF), a cytokine normally required for MCF-10A cell proliferation. This effect is blocked by the selective estrogen receptor modulator (SERM), Tamoxifen and the selective estrogen receptor downregulator, ICI 182,780 (Faslodex, Fulvestrant). Exposure of these cells to EGF and E2 results in a growth inhibitory phenotype similar to previous reports. These data present a reconciling explanation for the previously described paradoxical effects of ERα overexpression, and provide a model for examining the carcinogenic effects of estrogens in non-tumorigenic human breast epithelial cells.

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Acknowledgements

We thank Lizzy Weiner for technical assistance and members of the Park Lab for critical review of the manuscript. We also thank Cindy Zahnow and members of the Sukumar lab for helpful discussions regarding pharmacologic EGFR inhibition. We thank Dr Kornelia Polyak for the ERE GFP promoter/reporter vector.

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Authors and Affiliations

  1. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Abde M. Abukhdeir, Brian G. Blair, Keith Brenner, Bedri Karakas, Hiroyuki Konishi, Joselin Lim, Vanita Sahasranaman, Yi Huang, Judith Keen, Nancy Davidson & Ben Ho Park

  2. The Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA

    Michele I. Vitolo & Kurtis E. Bachman

  3. Department of Oncology, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 1M42, Baltimore, MD, 21231, USA

    Ben Ho Park

Authors
  1. Abde M. Abukhdeir
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  2. Brian G. Blair
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  3. Keith Brenner
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  4. Bedri Karakas
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  5. Hiroyuki Konishi
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  7. Vanita Sahasranaman
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  8. Yi Huang
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  9. Judith Keen
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  10. Nancy Davidson
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  11. Michele I. Vitolo
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  12. Kurtis E. Bachman
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  13. Ben Ho Park
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Corresponding author

Correspondence to Ben Ho Park.

Additional information

This work was supported by The Flight Attendant’s Medical Research Institute (FAMRI), The American Cancer Society (#IRG-58-005-41), NIH Breast SPORE Grant P50 CA88843, the Maryland Cigarette Restitution Fund, The Entertainment Industry Foundation, The Department of Defense Breast Cancer Research Program (DAMD17-03-1-0241), and the Avon Foundation. B.H.P. is an Avon Scholar for Breast Cancer Research and also receives generous support from The V Foundation for Cancer Research.

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Abukhdeir, A.M., Blair, B.G., Brenner, K. et al. Physiologic estrogen receptor alpha signaling in non-tumorigenic human mammary epithelial cells. Breast Cancer Res Treat 99, 23–33 (2006). https://doi.org/10.1007/s10549-006-9177-0

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  • DOI: https://doi.org/10.1007/s10549-006-9177-0

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