Long-term treatment with the pure anti-estrogen fulvestrant durably remodels estrogen signaling in BG-1 ovarian cancer cells. - Archive ouverte HAL Access content directly
Journal Articles Journal of Steroid Biochemistry and Molecular Biology Year : 2012

Long-term treatment with the pure anti-estrogen fulvestrant durably remodels estrogen signaling in BG-1 ovarian cancer cells.

(1) , (1) , (1) , (1) , (1, 2) , (1) , (1)
1
2

Abstract

Most ovarian cancers are estrogen-positive and hormonal treatments using anti-estrogens or aromatase inhibitors are under investigation for treating the tumors that are resistant to conventional therapies. In this study, the long-term effects of two anti-estrogens, namely 4-hydroxytamoxifen and fulvestrant (or ICI182,780), were investigated in ERα-positive BG1 epithelial ovarian cancer cells. To this aim, cells were grown in the presence of anti-estrogen concentrations that were sufficient to saturate the estrogen receptors, but were neither cytotoxic nor cytostatic as indicated by the absence of inhibition of cell proliferation. In these conditions and despite the lack of cytostatic effect of the drugs, long-term treatment (3 months) with the pure anti-estrogen fulvestrant induced a specific, reproducible and irreversible inhibition of ERα expression. This inhibition was accompanied by loss of estrogen-induced cell proliferation and gene expression as indicated by the analysis of several estrogen-responsive genes. ERα down-regulation was not linked to deregulated expression of transcription factors which drive ERα transcription and did not involve DNA methylation or histone deacetylation. Altogether, these results demonstrate that non-cytotoxic concentrations of pure anti-estrogens affect estrogen signaling and might be relevant for the treatment for ovarian cancers.
Fichier principal
Vignette du fichier
SBMB-Badia_E-VC.pdf (475.47 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

inserm-00705893 , version 1 (08-06-2012)

Identifiers

Cite

Eric Badia, Aurélie Docquier, Muriel Busson, Marion Lapierre, Pascal Pujol, et al.. Long-term treatment with the pure anti-estrogen fulvestrant durably remodels estrogen signaling in BG-1 ovarian cancer cells.. Journal of Steroid Biochemistry and Molecular Biology, 2012, 132 (1-2), pp.176-85. ⟨10.1016/j.jsbmb.2012.05.006⟩. ⟨inserm-00705893⟩
195 View
406 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More