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MRC Molecular Endocrinology Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK

(Requests for offprints should be addressed to S M Johnson; Email: smj4{at}le.ac.uk)

In this study, the oestrogen agonist/antagonist action of 4-hydroxytamoxifen (OHT; 1 x 10^–6 M) and 17ß-oestradiol (E₂; 1 x 10^–8 M) were assessed on the oestrogen receptor (ER)-positive epithelial cell line (Ishikawa) with respect to cell proliferation, and to gene and protein expression. qRT-PCR and western blotting confirmed that Ishikawa cells expressed both ER isoforms and that there was no change in transcript levels in response to either ligand. Gene expression profiles, using oligonucleotide arrays representing ~19 000 human genes, showed that the expression of 716 and 534 genes were changed differentially by treatment with either OHT or E₂ respectively, at the 24-h time point, with modulation of 46 genes common to both ligands, whereas 335 (OHT) and 240 (E₂) genes showed expression changes unique to ligand, with 13 common alterations at 48 h. Both OHT and E₂ had demonstrable oestrogen agonist actions on Ishikawa cells, exemplified by increased proliferation and expression of known oestrogen-responsive genes, such as creatine kinase B and by the induction of alkaline phosphatase activity. Additionally, the data indicate that the two oestrogen agonists generated not only common gene expression changes but also unique ligand-specific profiles, raising the intriguing possibility that tamoxifen has E₂-independent effects on the uterine epithelium.