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

Abde M. Abukhdeir, Brian G. Blair, Keith Brenner, Bedri Karakas, Hiroyuki Konishi, Joselin Lim, Vanita Sahasranaman, Yi Huang, Judith Keen, Nancy Davidson, Michele I. Vitolo, Kurtis E. Bachman, Ho Park Ben

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)23-33
Number of pages11
JournalBreast Cancer Research and Treatment
Volume99
Issue number1
DOIs
StatePublished - Sep 1 2006

Keywords

  • 17-beta-estradiol
  • Breast cancer
  • ERα
  • MCF-10A
  • Pre-neoplastic

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Abukhdeir, A. M., Blair, B. G., Brenner, K., Karakas, B., Konishi, H., Lim, J., Sahasranaman, V., Huang, Y., Keen, J., Davidson, N., Vitolo, M. I., Bachman, K. E., & Ben, H. P. (2006). Physiologic estrogen receptor alpha signaling in non-tumorigenic human mammary epithelial cells. Breast Cancer Research and Treatment, 99(1), 23-33. https://doi.org/10.1007/s10549-006-9177-0