The oestrogen-like effect of 4-hydroxytamoxifen on induction of transforming growth factor alpha mRNA in MDA-MB-231 breast cancer cells stably expressing the oestrogen receptor

Oestrogens and antioestrogens modulate the synthesis of transforming growth factor alpha (TGF-alpha) in breast cancer cells. The purpose of the presen t report was to examine regulation of TGF-alpha gene expression by oestradi ol (E2) and antioestrogens in MDA-MB-231 breast cancer cells transfected wi th either the wild-type or mutant oestrogen receptor (ER). We recently repo rted the concentration-dependent E2 stimulation of TGF-alpha mRNA in MDA-MB -231 ER transfectants (Levenson et al, 1997). We now report that 4-hydroxyt amoxifen (4-OHT) shows oestrogen-like effects on the induction of TGF-alpha gene expression in our transfectants, Accumulation of TGF-alpha mRNA in re sponse to both E2 and 4-OHT but not in response to the pure antioestrogen I CI 182,780 suggests that E2-ER and 4-OHT-ER complexes can bind to an oestro gen response element (ERE), located in the promoter region of the TGF-alpha gene and can activate transcription of the gene. Surprisingly, no activati on of luciferase expression was observed after transient transfection of th e TGF-alpha ERE/luciferase reporter constructs. Possible activation of an a lternative ER-mediated pathway responsible for the regulation of TGF-alpha gene expression in the ER transfectants is discussed.