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Resveratrol (Res) is a phytoestrogen found in grapes and present in red wine. Res has been shown to function as an estrogen receptor (ER) agonist, but it remains unclear whether it may also exert antagonist activity. Our aim was to study the effects of Res at both the molecular (TGF gene activation) and the cellular (cell growth) levels in breast cancer cells stably transfected with wild-type (wt) ER (D351) and mutant (mut) ER (D351Y). TGF mRNA induction was used as a specific marker of estradiol (E2) responsiveness. Res caused a concentration-dependent (10 8–10 4 M) stimulation of TGF mRNA, indicating that it acts as an estrogen agonist in these cell lines. The pure antiestrogen ICI 182,780 (ICI) blocked Res-induced activation of TGF, consistent with action through an ER-mediated pathway. Further studies that combined treatments with E2 and Res showed that Res does not act as an antagonist in the …