4.2 Article Proceedings Paper

Estrogen receptor-β activation in combination with letrozole blocks the growth of breast cancer tumors resistant to letrozole therapy

期刊

STEROIDS
卷 76, 期 8, 页码 792-796

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.steroids.2011.02.038

关键词

Breast cancer; Aromatase inhibitors; Drug resistance; Estrogen receptor beta agonists; Combination therapy

资金

  1. NIH/NCI [R01 CA75018, P30 CA54714]
  2. V foundation

向作者/读者索取更多资源

Treatment with anti-estrogens or aromatase inhibitors (AI) is the main therapeutic strategy used against estrogen receptor ER alpha-positive breast cancer. Resistance to these therapies presents a major challenge in the management of breast cancer. Little is known about ER beta in breast carcinogenesis. Our aim in this study is to examine potential novel strategies utilizing ER beta activity to overcome AI resistance. We provide evidence that ER 0 agonist can reduce the growth of AI-resistant breast cancer cells. Our data further confirm that therapeutic activation of ER beta by DPN, an ER beta agonist, blocks letrozole-resistant tumor growth in a xenograft model. interestingly. DPN exerted tumor growth inhibition only in the presence of the AI letrozole, suggesting that combination therapy including ER beta activators and AI may be used in the clinical setting treating AI resistant breast cancer. An increase in ER beta levels, with diminished ER alpha/ER beta ratio, was observed in the tumors from mice treated with DPN/letrozole combination compared to single agents and control. Decreased Cyclin D1 and increased CyclinD1/CDK inhibitors p21 and p27 levels in DPN/letrozole treated tumors were observed, suggesting that the combination treatment may inhibit tumor growth by blocking G1/S phase cell cycle progression. Our data show a decrease in MAPK phosphorylation levels without affecting total levels. In addition to providing evidence suggesting the potential use of ER beta agonists in combination with letrozole in treating AI resistant breast cancer and prolonging sensitivity to AI. we also provide mechanistic evidence supporting the role of ER beta in altering the expression profile associated with resistance. (C) 2011 Elsevier Inc. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.2
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据