کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1991594 | 1541019 | 2012 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Long-term treatment with the pure anti-estrogen fulvestrant durably remodels estrogen signaling in BG-1 ovarian cancer cells Long-term treatment with the pure anti-estrogen fulvestrant durably remodels estrogen signaling in BG-1 ovarian cancer cells](/preview/png/1991594.png)
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.
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► We study the effects of long-term antiestrogen treatments on cancer ovary cells.
► Non cytotoxic/cytostatic doses of antiestrogens are used.
► We study the phenotypic remodeling induced by antiestrogen treatment.
► We compare effects of 4-hydroxytamoxifen and ICI182,780 (fulvestrant).
► Fulvestrant but not 4-hydroxytamoxifen induces an irreversible inhibition of ERalpha.
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 132, Issues 1–2, October 2012, Pages 176–185