Antiprogestins prevent progesterone receptor binding to hormone responsive elements in vivo.
AUTOR(ES)
Truss, M
RESUMO
Antiprogestins inhibit progesterone action by competing for binding to the progesterone receptor and are potentially important pharmaceuticals in fertility control and cancer therapy. Why the complex of antiprogestins and progesterone receptor is functionally inactive is unclear. Present models are based on indirect evidence, such as transfection competition assays and in vitro DNA binding studies, partly because of difficulties in visualizing the receptor bound to DNA in vivo. Here we used genomic footprinting analysis to show ligand-dependent binding of endogenous progesterone receptor to the hormone responsive elements (HREs) of a chromosomally integrated mouse mammary tumor virus long terminal repeat in a human mammary carcinoma cell line. The antiprogestins RU 486 and ZK 98299 do not promote binding of the progesterone receptor to this natural HRE in vivo, even at concentrations that completely inhibit the agonistic effects of potent synthetic progestins. Moreover, antiprogestins cause a rapid disappearance of the agonist-induced progesterone receptor footprint. We conclude that antiprogestins interfere with receptor function by preventing its specific DNA binding.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=45225Documentos Relacionados
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