期刊文献

Antiproliferative actions of the synthetic androgen, mibolerone, in breast cancer cells are mediated by both androgen and progesterone receptors 收藏

乳腺癌细胞中合成雄激素Mibolerone的抗增生作用均由雄激素和孕激素受体介导
原文求助 发布源
作者
Elisa J.Cops[a];TinaBianco-Miotto[a];Nicole L.Moore[a][1];Christine L.Clarke[b];Stephen N.Birrell[a];Lisa M.Butler[a];Wayne D.Tilley[a];
作者单位
[a]Dame Roma Mitchell Cancer Research Laboratories, Discipline of Medicine, University of Adelaide and Hanson Institute, Adelaide, South Australia, 5000, Australia[b]Westmead Institute for Cancer Research, Westmead Hospital, Westmead, New South Wales, 2145, Australia[1]Present address: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
关键词
Breast cancer; Androgens; DHT; Mibolerone; MPA; Androgen receptor; Progesterone receptor;
关键词译文
乳腺癌;雄激素；DHT;mibolerone;mpa;雄激素受体；孕酮受体；
发布日期
1 June 2008
DOI
10.1016/j.jsbmb.2007.10.014
来源信息
The Journal of Steroid Biochemistry and Molecular Biology ISSN：0960-0760, 2008年, 110卷, 3-5期
摘要
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 5α-dihydrotestosterone (DHT) and a synthetic androgen, mibolerone, on estradiol (E2)-induced proliferation of breast cancer cells. DHT modestly inhibited E2-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 (10–100 nM) of DHT reduced E2-mediated induction of the estrogen-regulated gene progesterone receptor (PR) to basal levels, mibolerone at lower doses (1 nM) 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 E2-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.
摘要译文
由雄激素受体（AR）介导的雄激素信号传导是影响正常和恶性乳腺细胞生长的关键因素。鉴于女性中外源性雄激素的使用越来越多，对乳房中雄激素作用的更好理解至关重要。这项研究比较了5α-二氢睾丸激素（DHT）和合成雄激素Mibolerone对雌二醇（E 2）诱导的乳腺癌细胞增殖的影响。DHT适度抑制E 2诱导的增殖和Mibolerone可显着抑制T -47D细胞的增殖。两种雄激素的影响都可以由AR拮抗剂逆转，这表明它们的作用是由AR介导的。DHT的高生理剂量（10-100 nm）降低E 2介导的雌激素调节基因孕酮受体（PR）诱导至基础水平，而较低剂量（1 nm）的Mibolerone消除了PR的表达，这表明Mibolerone也可能也可能也可能通过公关行动。在AR阳性，PR-PR-DEG-7细胞中，Mibolerone对E 2诱导的增殖具有适度的影响，但在AR阳性，PR阳性MCF-7M11 PRA细胞中是增殖的有效抑制剂。Mibolerone在乳腺癌细胞中的作用与孕激素甲乙酸甲酸酸酯的作用相似。我们的结果表明，Mibolerone可以在乳腺癌细胞中同时具有雄激素和孕激素作用。
Elisa J.Cops[a];TinaBianco-Miotto[a];Nicole L.Moore[a][1];Christine L.Clarke[b];Stephen N.Birrell[a];Lisa M.Butler[a];Wayne D.Tilley[a];. Antiproliferative actions of the synthetic androgen, mibolerone, in breast cancer cells are mediated by both androgen and progesterone receptors[J]. The Journal of Steroid Biochemistry and Molecular Biology, 2008,110(3-5)