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Characterization of the weak estrogen receptor α agonistic activity of exemestane

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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.

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Notes

  1. http://research.i2r.a-star.edu.sg/kberg/.

  2. http://bioinformatics.med.ohio-state.edu/ERTargetDB/.

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Acknowledgement

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

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Authors and Affiliations

  1. Department of Surgical Research, Beckman Research Institute of the City of Hope, 1500 E Duarte Road, Duarte, CA, 91010, USA

    Selma Masri, Ki Lui, Sheryl Phung, Jingjing Ye, Dujin Zhou, Xin Wang & Shiuan Chen

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  1. Selma Masri
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Correspondence to Shiuan Chen.

Additional information

Microarray data in this publication has been deposited in NCBIs Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) and is accessible through GEO Series accession number GSE10911.

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Masri, S., Lui, K., Phung, S. et al. Characterization of the weak estrogen receptor α agonistic activity of exemestane. Breast Cancer Res Treat 116, 461–470 (2009). https://doi.org/10.1007/s10549-008-0151-x

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