PD98059 blocks phosphorylation and activation of MAPK proteins, ERK1 and ERK2. In the course of examining the effect of PD98059 on estrogen-induced transcription of reporter genes in a human breast cancer cell line and in yeast, we found that two of four different batches of PD98059 produced estrogenic effects in a dose-dependent manner. In a competitive binding assay, these preparations of PD98059 displaced radiolabeled estradiol from ERα. Furthermore, in the yeast assay, addition of a coactivator protein, AIB1, enhanced the transcriptional effect of PD98059, indicating that it induces receptor-coactivator interactions. Although concentrations of PD98059 required to activate ERα in these experimental systems are 104 to 105 higher than the concentration of estradiol required to do the same, the concentrations required to block MAPK activation are well above those which would produce maximal estrogenic effects. Thus, when PD98059 is used in estrogen-responsive cells, contaminating estrogenic activity may confound interpretation of experimental results.
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