Effects of oestrogen and the antioestrogens, tamoxifen and LY117018, on four oestrogen-regulated RNAs in the EFM-19 breast cancer cell line.
The EFM-19 cell line is a new breast cancer cell line whose proliferation has been reported to be stimulated by oestrogens and inhibited by the antioestrogen tamoxifen. Oestrogen receptor mRNA levels are higher in EFM-19 cells than in other oestrogen-responsive cell lines. The levels of four oestrogen-inducible RNAs [pNR-1, pNR-2, pNR-25 and pNR-100] were measured in EFM-19 cells. Oestradiol treatment increased the levels of the four regulated RNAs between 3-fold (pNR-100) and greater than 100-fold (pNR-2). The induction was half maximal between 1.5 x 10(-11) and 1.5 x 10(-10) M oestradiol. The effects of two antioestrogens, tamoxifen and LY117018, were measured on the expression of the oestrogen-regulated RNAs. Tamoxifen was a partial oestrogen agonist for the induction of the pNR-1 and pNR-25 RNAs but had very little effect on the pNR-2 and pNR-100 RNA levels. The pNR-2 RNA levels were less induced by tamoxifen in EFM-19 cells than in MCF-7 cells. LY117018 did not increase the levels of any RNA. The oestrogen-induced levels of the four RNAs were reduced by both antioestrogens to the RNA levels present in cells treated with the antioestrogens alone. LY117018 was at least 100-fold more potent than tamoxifen as an oestrogen antagonist.
Westley
B R
BR
University Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, England.
Hölzel
F
F
May
F E
FE
D001943:Breast Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009693:Nucleic Acid Hybridization; D011759:Pyrrolidines / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis* / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D011960:Receptors, Estrogen / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D011759:Pyrrolidines; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013876:Thiophenes; D013629:Tamoxifen; D004958:Estradiol; D012313:RNA; C025430:LY 117018