Selective modulation of ER-β by estradiol and xenoestrogens in human breast cancer cell lines

Abstract.

In the last decades, substances with estrogenic activity have been dispersed into the environment. Xenoestrogens act by binding to estrogen receptors, ligand-regulated transcription factors, for which two subtypes have been described, Er-α and Er-β, which are often coexpressed at variable amounts in different tissues. We investigated variations in the expression of Er-α and Er-β mRNAs following treatment with four xenoestrogens (bisphenol A, 4-tert octylphenol, 2-hydroxybiphenyl, 4-hydroxybiphenyl) and with 17β-estradiol in estrogen-sensitive (T47D) and estrogen-insensitive (BT20) breast cancer cell lines. Although to a variable extent, both estradiol and the tested xenoestrogens increased the expression of Er-β mRNA, whereas a slight effect on Er-α was observed only in T47D cells. Upregulation of Er-β expression by estradiol and xenoestrogens was observed only in the presence of detectable Er-α protein levels. These findings indicate a regulatory role for ER-β in ER-α-mediated transcription and a role for ER-β in mediating xenoestrogen toxicity.