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Type: Journal article
Title: Antiproliferative actions of the synthetic androgen, mibolerone, in breast cancer cells are mediated by both androgen and progesterone receptors
Author: Cops, E.
Bianco-Miotto, T.
Moore, N.
Clarke, C.
Birrell, S.
Butler, L.
Tilley, W.
Citation: Journal of Steroid Biochemistry and Molecular Biology, 2008; 110(3-5):236-243
Publisher: Pergamon-Elsevier Science Ltd
Issue Date: 2008
ISSN: 0960-0760
Statement of
Elisa J. Cops, Tina Bianco-Miotto, Nicole L. Moore, Christine L. Clarke, Stephen N. Birrell, Lisa M. Butler and Wayne D. Tilley
Abstract: Androgen signaling, mediated by the androgen receptor (AR), is a critical factor influencing growth of normal and malignant breast cells. Given the increasing use of exogenous androgens in women, a better understanding of androgen action in the breast is essential. This study compared the effects of 5alpha-dihydrotestosterone (DHT) and a synthetic androgen, mibolerone, on estradiol (E(2))-induced proliferation of breast cancer cells. DHT modestly inhibited E(2)-induced proliferation and mibolerone significantly inhibited proliferation in T-47D cells. The effects of both androgens could be reversed by an AR antagonist, suggesting that their actions were mediated, in part, by AR. Whereas high physiological doses (10-100nM) of DHT reduced E(2)-mediated induction of the estrogen-regulated gene progesterone receptor (PR) to basal levels, mibolerone at lower doses (1nM) eliminated PR expression, suggesting that mibolerone may also act via the PR. In the AR positive, PR-negative MCF-7 cells, mibolerone had modest effects on E(2)-induced proliferation, but was a potent inhibitor of proliferation in the AR positive, PR positive MCF-7M11 PRA cells. The effects of mibolerone in breast cancer cells were similar to those of the progestin, medroxyprogesterone acetate. Our results demonstrate that mibolerone can have both androgenic and progestagenic actions in breast cancer cells.
Keywords: Tumor Cells, Cultured; Humans; Breast Neoplasms; Dihydrotestosterone; Estradiol; Nandrolone; Testosterone Congeners; Receptors, Androgen; Receptors, Progesterone; Androgens; Progestins; Drug Evaluation, Preclinical; Cell Proliferation; Medroxyprogesterone Acetate
Description: Copyright © 2008 Elsevier Ltd All rights reserved.
RMID: 0020081525
DOI: 10.1016/j.jsbmb.2007.10.014
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