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Breast Cancer Res Treat. 2009 Jun;115(3):523-35. doi: 10.1007/s10549-008-0094-2. Epub 2008 Jun 19.

Association between farnesoid X receptor expression and cell proliferation in estrogen receptor-positive luminal-like breast cancer from postmenopausal patients.

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  • 1Laboratory of Endocrinology & Translational Research Unit, Department of Internal Medicine, Institut Jules Bordet, Universit√© Libre de Bruxelles, Brussels, Belgium. fabrice.journe@bordet.be

Abstract

The farnesoid X receptor (FXR, NR1H4), a member of the nuclear receptor superfamily of ligand-dependent transcription factors, is normally produced in the liver and the gastrointestinal tract, where it acts as a bile acid sensor. It has been recently detected in breast cancer cell lines and tissue specimens. The expression of FXR was scored (0-8) by immunohistochemistry on 204 breast cancer samples and correlated with established cancer biomarkers. Moreover, the effect of the FXR activator chenodeoxycholic acid (CDCA) was determined on cell proliferation and estrogen receptor regulation/activation in breast cancer cell lines. FXR was detected in 82.4% of samples with a high median expression score of 5. FXR expression significantly correlated with estrogen receptor (ER) expression (P = 0.009) and luminal-like markers. In ER-positive tumors, FXR expression was significantly correlated with the proliferation marker Ki-67 (P < 0.001) and the nodal status (P = 0.028), but only so in postmenopausal women, suggesting that lack of estrogens may disclose the association between FXR and cell proliferation. In vitro experiments confirmed clinical data since CDCA stimulated the proliferation of ER-positive cells only in steroid-free medium, a stimulation inhibited upon siRNA-silencing of FXR expression as well as ER blockade by antiestrogens. Moreover, co-immunoprecipitation experiments revealed that CDCA activated-FXR interacted with ER. These results suggest that ER-positive breast tumors could be stimulated to proliferate via a crosstalk between FXR and ER, particularly in a state of estrogen deprivation (menopause, aromatase inhibitors).

PMID:
18563553
DOI:
10.1007/s10549-008-0094-2
[PubMed - indexed for MEDLINE]
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