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Oestrogens and antioestrogens modulate the synthesis of transforming growth factor alpha (TGF-alpha) in breast cancer cells. The purpose of the present report was to examine regulation of TGF-alpha gene expression by oestradiol (E2) and antioestrogens in MDA-MB-231 breast cancer cells transfected with either the wild-type or mutant oestrogen receptor (ER). We recently reported the concentration-dependent E2 stimulation of TGF-alpha mRNA in MDA-MB-231 ER transfectants (Levenson et al, 1997). We now report that 4-hydroxytamoxifen (4-OHT) shows oestrogen-like effects on the induction of TGF-alpha gene expression in our transfectants. Accumulation of TGF-alpha mRNA in response to both E2 and 4-OHT but not in response to the pure antioestrogen ICI 182,780 suggests that E2-ER and 4-OHT-ER complexes can bind to an oestrogen response element (ERE), located in the promoter region of the TGF …