Binding studies of RU486 in different Reuber hepatoma variants.
The synthetic steroid RU486, which displays antiprogestin and antiglucocorticoid properties in different systems, inhibits cell growth in dexamethasone-sensitive H56 cells containing glucocorticoid receptors, as well as in dexamethasone-resistant S-H56-125 cells displaying a very low level of dexamethasone binding. In order to better understand the mechanism of the antiproliferative effect, the binding of RU486 to these hepatoma cells was examined. Results revealed the presence of two different kinds of binding sites for RU486 in dexamethasone-sensitive H56 cells whereas only one type of site was detected in the dexamethasone-resistant cells. These peculiar sites were also recognized by cortivazol during competition experiments. Thus, it seems that S-H56-125 cells contain an altered glucocorticoid receptor that binds RU486 and cortivazol but virtually not dexamethasone. The ability of RU486 to inhibit the growth of dexamethasone-resistant cells suggests this steroid may be used to treat tumor cells that develop glucocorticoid resistance after long-term treatment.
Chasserot-Golaz
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S
Unité Propre de Recherche No 9002 du CNRS, Strasbourg, France.
Beck
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G
D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000378:metabolism; D014644:Genetic Variation; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D015735:Mifepristone / Q000378:metabolism*; D011281:Pregnatrienes / Q000378:metabolism / Q000494:pharmacology; D011397:Promegestone / Q000378:metabolism; D051381:Rats; D011987:Receptors, Steroid / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011281:Pregnatrienes; D011987:Receptors, Steroid; D015735:Mifepristone; D013739:Testosterone; D003907:Dexamethasone; D011397:Promegestone; C005924:cortivazol