Zusammenfassung
Coexpression of estrogen receptors (ER) alpha and beta is present in about half of all breast cancer cases. Whereas ER alpha is a well-established target for endocrine therapy with the selective estrogen receptor modulator tamoxifen, the applicability of ER beta as target in breast cancer therapy is unclear. In this study, we examined the effects of two synthetic ER beta agonists alone and in ...
Zusammenfassung
Coexpression of estrogen receptors (ER) alpha and beta is present in about half of all breast cancer cases. Whereas ER alpha is a well-established target for endocrine therapy with the selective estrogen receptor modulator tamoxifen, the applicability of ER beta as target in breast cancer therapy is unclear. In this study, we examined the effects of two synthetic ER beta agonists alone and in combination with tamoxifen on ER alpha/beta-positive breast cancer cells. We treated MCF-7 and T-47D breast cancer cells with the ER beta agonists ERB-041 and WAY-200070 and measured the effects on cell growth. In addition, transcriptome analyses were performed by means of Affymetrix GeneChip arrays. When given alone, ER beta agonists ERB-041 and WAY-200070 did not affect the growth of MCF-7 or T-47D cells. In contrast, addition of these drugs to tamoxifen increased its growth-inhibitory effect on both cell lines. This effect was more pronounced under serum-free conditions, but was also observed in the presence of serum in T-47D cells. Transcriptome analyses revealed a set of genes regulated after addition of ER beta agonists including S100A8 and CD177. The observed enhanced growth-inhibitory effects of a combination of tamoxifen and ER beta agonists in vitro encourage further studies to test its possible use in the clinical setting.
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