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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)461-470
Number of pages10
JournalBreast Cancer Research and Treatment
Volume116
Issue number3
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Aromatase inhibitors
  • Estrogen receptor
  • Exemestane

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