Bisphenol AF as an activator of human estrogen receptor beta 1 (ER beta 1) in breast cancer cell lines

摘要

Bisphenol AF (BPAF) is now recognized as one of the replacements for bisphenol A (BPA). Although considerable experimental evidence suggests that BPA is an endocrine-disrupting chemical, the toxicological profile of BPAF has been investigated in less detail than that of BPA, even at the in vitro level. BPAF has been established as an activator of estrogen receptor alpha (ER alpha) in many cell lines; however, controversy surrounds its effects on the other isoform, ER beta (i.e., whether it functions as a stimulator). Five human ER beta isoforms have been cloned and characterized. Of these, we focused on the interactions between BPAF and the two isoforms, ER beta 1 and ER beta 2. We demonstrated that i) BPAF functioned as a stimulator of ER beta 1 (and ER alpha), which is transiently expressed in the two types of human breast cancer cells (MDA-MB-231 and SK-BR-3 cells) (E-50 values for ER beta: 6.87 nM and 2.58 nM, respectively, and EC50 values for ERa: 24.7 nM and 181 nM, respectively), ii) the stimulation of ER beta 1 by BPAF (1-25 nM) was abrogated by PHTPP (an ER beta selective antagonist), and iii) the expression of ER beta 1 and ER beta 2 was not modulated by BPAF at nanomolar concentrations up to 25 nM. These results indicate that BPAF activates not only human ER alpha, but also the ER beta 1 isoform in breast cancer cells, and exhibits higher activation potency for ER beta 1.