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• W2073169219 abstract "Estrogens act as potent mitogens in a large number of breast cancers, and the use of estrogen receptor (ER) antagonists is, therefore, considered the endocrine therapy of choice in the management of this disease. We describe the molecular properties of EM-652, the active metabolite of EM-800, a novel nonsteroidal antiestrogen compound, on the transcriptional functions of ERα and ERβ. Using RT-PCR, we show that ERα and ERβ are expressed in mouse mammary glands, suggesting that both receptors should be considered putative targets for antiestrogen action in the breast. In cotransfection assays using a synthetic estrogen-responsive promoter, EM-652 shows no agonistic activity on ERα and ERβ transcriptional function and blocks the estradiol (E2)-mediated activation of both ERα and ERβ. EM-652 is also very effective in abrogating E2-stimulated ERα and ERβ trans-activation of the pS2 promoter in HeLa cells. EM-652 does not alter binding of ERα and ERβ to DNA. The Ras-mediated induction of ERα and ERβ transcriptional activity in the presence of E2 is also completely abolished by EM-652. In addition, EM-652 blocks the E2-dependent activation of ERα and ERβ by the steroid hormone receptor coactivator-1 as well as the in vitro interaction between SRC-1 and the ligand-binding domains of both ERs. These results demonstrate that the novel antiestrogen EM-800 fully impedes AF-1 and AF-2 activities of ERα and ERβ and can, therefore, be considered a potent and pure antagonist of both ER subtypes." @default.
• W2073169219 created "2016-06-24" @default.
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• W2073169219 date "1998-01-01" @default.
• W2073169219 modified "2023-10-01" @default.
• W2073169219 title "EM-800, a Novel Antiestrogen, Acts as a Pure Antagonist of the Transcriptional Functions of Estrogen Receptors α and β*" @default.
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• W2073169219 doi "https://doi.org/10.1210/endo.139.1.5702" @default.
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