Breast Cancer Research and Treatment

, Volume 116, Issue 3, pp 461–470 | Cite as

Characterization of the weak estrogen receptor α agonistic activity of exemestane

  • Selma Masri
  • Ki Lui
  • Sheryl Phung
  • Jingjing Ye
  • Dujin Zhou
  • Xin Wang
  • Shiuan Chen
Preclinical Study


Third generation aromatase inhibitors (AI) have shown good clinical efficacy in comparison to the anti-estrogen tamoxifen. The steroidal AI, exemestane (EXE) has previously been shown to act as an androgen, but this report demonstrates the estrogen-like activity of EXE. Based on genome-wide microarray analysis, high correlation was seen between EXE-Only (EXE O, hormone-free) and hormone-containing AI-resistant lines. In addition, the top regulated genes in the EXE O lines were mostly estrogen-responsive genes. This estrogen-like activity of EXE was further validated using estrogen receptor (ER) activity assays, where in comparison to 17β-estradiol (E2), EXE was able to induce ER activity, though at a higher concentration. Also, this EXE-mediated ER activity was blocked by the ER antagonist ICI as well as the ERα-specific antagonist methyl-piperidino-pyrazole (MPP). Similarly, EXE was able to induce proliferation of breast cancer cell lines, MCF-7 and MCF-7aro, as well as activate transcription of known estrogen-responsive genes, i.e., PGR, pS2 and AREG. These results suggest that EXE does have weak estrogen-like activity.


Aromatase inhibitors Exemestane Estrogen receptor 



S. Masri was supported by NIH pre-doctoral training fellowship CA123691 and S. Chen by NIH grants CA044735 and ES08258.


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Selma Masri
    • 1
  • Ki Lui
    • 1
  • Sheryl Phung
    • 1
  • Jingjing Ye
    • 1
  • Dujin Zhou
    • 1
  • Xin Wang
    • 1
  • Shiuan Chen
    • 1
  1. 1.Department of Surgical ResearchBeckman Research Institute of the City of HopeDuarteUSA

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