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- W2118728497 abstract "Estrogen receptors (α and ß) are members of the steroid/thyroid nuclear receptors superfamily of ligand-dependent transcription factors. Impact of the ? isoform of estrogen receptor (ER) on breast cancer etiology and progression is now well established. Current therapeutic strategy to treat ER-positive breast cancer relies on the blockade of ER trancriptional activity by antiestrogens. Data accumulated during the last five years on the mechanism of action of ER enable one to foresee new strategies. These data indeed reveal that ER is not statically bound to DNA at promoter sites of genes regulating cell proliferation and/or differentiation, but rather behaves as a very mobile protein continuously shuttling between targets located within various cellular compartments (i.e. membrane, microsomes, nucleus...). This allows the receptor to generate both non-genomic and genomic responses. Ligands, growth factors and second messengers produced downstream of activated membrane receptors modulate ER-mediated responses by interfering with the traffic patterns of the receptor, as well as by locally blocking its transient anchorage. Changes in ER turnover rate associated with these regulatory processes seem also to strongly influence the ability of the receptor to mediate gene transactivation. The present paper surveys these biological data and analyzes how they may be integrated into new drug design programs aimed at expanding our therapeutic armamentarium against breast cancer. Keywords: Estrogen receptor α, shuttling, trafficking, turnover, proteasome, breast cancer, transcription, signal transduction" @default.
- W2118728497 created "2016-06-24" @default.
- W2118728497 creator A5057359381 @default.
- W2118728497 creator A5068390664 @default.
- W2118728497 creator A5075593404 @default.
- W2118728497 creator A5082934839 @default.
- W2118728497 date "2006-02-01" @default.
- W2118728497 modified "2023-10-18" @default.
- W2118728497 title "Estrogen Receptor Alpha: Impact of Ligands on Intracellular Shuttling and Turnover Rate in Breast Cancer Cells" @default.
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