title: Antiprogestin-receptor complexes: differences in the interaction of the antiprogestin RU38,486 and the progestin R5020 with the progesterone receptor of human breast cancer cells.
abstract: In order to understand the molecular basis for antiprogestin action, we have compared the interaction of the antiprogestin [3H]RU38, 486 (RU486) and the progestin [3H]R5020 with the progesterone receptor (PR). In both MCF-7 and T47D human breast cancer cells, we have observed marked differences in the sedimentation properties of the PR on high salt sucrose gradients: while the R5020-receptor complexes sediment at approximately 4 S (4.4 +/- 0.1 S), the RU486-receptor sediments as a prominent 6 S species as well as a 4 S species. This binding is abolished by excess unlabelled R5020, RU486 or progesterone, but is unaffected by excess unlabelled hydrocortisone or dexamethasone, indicating that both the 4 S and 6 S species represent the PR and not glucocorticoid receptor. Although the relative distribution of 4 S and 6 S forms is not altered by treatment with DNAse or RNAse, exposure to 10 mM thioglycerol or to 3 M urea results in conversion of the 6 S to the 4 S form, suggesting that disulfide bonds and hydrophobic interactions are important in maintaining the integrity of the 6 S form. These findings suggest that the 6 S antiprogestin complex is formed as a result of the interaction of PR units with each other or with a different protein. This change in receptor association state may be an important aspect of the antiprogestin activity of RU486.
mesh_terms: D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D003851:Deoxyribonucleases / Q000378:metabolism; D004963:Estrenes / Q000378:metabolism*; D005260:Female; D006801:Humans; D015735:Mifepristone; D009649:Norpregnadienes / Q000378:metabolism*; D011397:Promegestone / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014508:Urea / Q000494:pharmacology
chemical_list: D004963:Estrenes; D009649:Norpregnadienes; D011980:Receptors, Progesterone; D013438:Sulfhydryl Compounds; D015735:Mifepristone; D014508:Urea; D011397:Promegestone; D003851:Deoxyribonucleases; D012260:Ribonucleases