Raloxifene inhibits menin-dependent estrogen receptor activation in breast cancer cells

被引:0
|
作者
H. Imachi
X. Yu
T. Nishiuchi
Y. Miyai
H. Masugata
K. Murao
机构
[1] Kagawa University,Department of Advanced Medicine, Faculty of Medicine
[2] Soochow University,Laboratory of Cellular and Molecular Tumor Immunology, Medical College
[3] Kagawa University,Department of Diagnostic Pathology, Faculty of Medicine
[4] Kagawa University,Department of Integrated Medicine, Faculty of Medicine
来源
Journal of Endocrinological Investigation | 2011年 / 34卷
关键词
Breast cancer; estrogen receptor; menin; raloxifene; tamoxifen;
D O I
暂无
中图分类号
学科分类号
摘要
Background: Menin is a tumor suppressor encoded by Men1 that is mutated in the human-inherited tumor syndrome — multiple endocrine neoplasia type 1. Menin binds to estrogen receptors (ER) to enhance estrogen activity in breast cancer cells. Aim: Our clinical study showed that the outcome in the case of menin-positive tumors was worse than in the case of menin-negative tumors. We examined the role of raloxifene on the cell growth in a menin-positive breast cancer cell line. Material and methods: To examine the mechanism of raloxifene on menin-dependent activation of ER, we employed the mammalian two-hybrid system. We have established a breast cancer cell line that stably expresses menin. Using these cells, we have examined the effect of raloxifene and tamoxifen on cell growth of menin-transfected cells. Results: The expression of activation function (AF)-2 enhanced menin-mediated luciferase expression in the mammalian two-hybrid assay. Raloxifene attenuated the effect of menin on estrogen response element-luciferase activation, indicating that raloxifene inhibited the binding of menin to AF-2. Raloxifene significantly inhibited the growth of menin-transfected cells in a dose-dependent manner. Tamoxifen also inhibited menin-transfected MCF-7 cells; however, this inhibition was much less than that of raloxifene. Conclusion: Raloxifene inhibits the binding of menin to the AF-2 domain of ERα, suggesting that raloxifene is one of the therapeutic options for menin-positive breast cancer.
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页码:813 / 815
页数:2
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