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Breast Cancer Research and Treatment

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01.08.2009 | Preclinical Study

Characterization of the weak estrogen receptor α agonistic activity of exemestane

verfasst von: Selma Masri, Ki Lui, Sheryl Phung, Jingjing Ye, Dujin Zhou, Xin Wang, Shiuan Chen

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2009

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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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Titel: Characterization of the weak estrogen receptor α agonistic activity of exemestane
verfasst von: Selma Masri
Ki Lui
Sheryl Phung
Jingjing Ye
Dujin Zhou
Xin Wang
Shiuan Chen
Publikationsdatum: 01.08.2009
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2009
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0151-x

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