title: Effects of tamoxifen and 4-hydroxytamoxifen on the pNR-1 and pNR-2 estrogen-regulated RNAs in human breast cancer cells.
abstract: The estrogenic and antiestrogenic activities of tamoxifen and 4-hydroxytamoxifen have been measured on the expression of two estrogen-regulated RNAs (pNR-1 and pNR-2) in the MCF7 human breast cancer cell line cultured in phenol red-free medium. The two antiestrogens increased the level of the pNR-1 RNA to about 80% of the estradiol-induced level, and the induction by estradiol was not significantly antagonized by either antiestrogen. In contrast, the pNR-2 mRNA was only increased to about 10% of the estradiol-induced level, and its induction by estradiol was antagonized by both tamoxifen and 4-hydroxytamoxifen. Thus, the two RNAs respond in dramatically different ways to these antiestrogens. 4-Hydroxytamoxifen and estradiol have similar affinities for the estrogen receptor; however, the induction of both RNAs by 4-hydroxytamoxifen required a 10-fold higher concentration than estradiol for maximum agonist activity, and a 500-fold molar excess was required to antagonize the induction by estradiol. Tamoxifen has a 20-100-fold lower affinity than estradiol for the estrogen receptor. A 200-fold higher concentration was required for maximum agonist activity and a 10,000-fold molar excess to antagonize the induction by estradiol. These results emphasize the complexity of antiestrogen action in human breast cancer cells.
authors.affiliation: Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: F E
authors.initials: FE
authors.lastname: May
authors.forename: B R
authors.initials: BR
authors.lastname: Westley
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004262:DNA Restriction Enzymes; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004965:Estrogen Antagonists; D012333:RNA, Messenger; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D004262:DNA Restriction Enzymes