The selective oestrogen receptor modulators idoxifene and raloxifene have fundamentally different cell-specific oestrogen-response element (ERE)-dependent/independent mechanisms in vitro.
Idoxifene and raloxifene are selective oestrogen receptor modulators (SERMs) that by definition exhibit tissue-specific agonist or antagonist properties via interactions with the oestrogen receptor (ER). Idoxifene acts as an oestrogen agonist in osteoblastic cells via an ER/ERE-mediated mechanism. In contrast, raloxifene is an antagonist via the ERE in osteoblastic cells. Like the pure antagonist ICI 182,780, raloxifene inhibited the potent agonist activity of both 17beta-oestradiol and idoxifene through the ERE whereas idoxifene had no effect on the agonist activity of 17beta-oestradiol via the ERE. In breast cancer cells, both raloxifene and idoxifene were potent antagonists of ERE-mediated 17beta-oestradiol action suggesting an ERE-dependent mechanism of action for both ligands in these cells. Therefore, these SERMs exhibit cell-specific ERE-dependent and -independent mechanisms of action.
Nuttall
M E
ME
Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, UW2109, 709 Swedeland Road, PO Box 1539, King of Prussia, PA 19406, USA. mark_e_nuttall@sbphrd.com
Fisher
P W
PW
Suva
L J
LJ
Gowen
M
M
D001943:Breast Neoplasms / Q000378:metabolism; D002455:Cell Division; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012097:Repressor Proteins; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004965:Estrogen Antagonists; D004967:Estrogens; D012097:Repressor Proteins; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C071362:idoxifene; D020849:Raloxifene Hydrochloride