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J Endocrinol Invest. 2011 Dec;34(11):813-5.

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

Author information

1
Department of Advanced Medicine, Faculty of Medicine, Kagawa University, 1750-1 Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

Abstract

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 ERĪ±, suggesting that raloxifene is one of the therapeutic options for menin-positive breast cancer.

PMID:
22322533
DOI:
10.1007/BF03346730
[Indexed for MEDLINE]

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