Perfluorinated Iodine Alkanes Induce Tissue-Specific Expression Of Estrogen Receptor And Its Phosphorylation

Understanding the tissue-specific regulation of environmental endocrine disrupting chemicals (EDCs) on the expression and phosphorylation of estrogen receptors (ERs) is essential to fully reveal their perturbation in endocrine system. In the present study, two kinds of perfluorinated iodine alkanes (PFIs) with estrogenic activities, i.e. tridecafluorohexyl iodide (PFHxI) and dodecafluoro-1,6-diiodohexane (PFHxDI), were studied for their effects on the expressions and the phosphorylation of ER isoforms (i.e. ER alpha and ER beta) in three types of human-derived cell lines (i.e. breast cancer MCF-7 cells, breast ductal carcinoma T47D cells, and liver hepatocellular carcinoma HepG2 cells). The endogenous estrogen, 17 beta-estradiol (E-2) was concomitantly tested as the positive control. The results showed that both ER alpha and ER beta were expressed in three test cell lines, wherein, breast tissues contained relatively higher levels of ER isoforms than did hepatic cells. The treatment of E-2 reduced expressions of both ER isoforms, and induced phosphorylation of ER alpha in MCF-7 and T47D cells. The exposure of PFHxI and PFHxDI decreased the transcriptional levels of both ER isoforms in MCF-7, while only PFHxI caused a reduction of ER beta mRNA expression in T47D. The phosphorylation of ER alpha was elevated in MCF-7 upon PFHxI treatment. These findings firstly uncovered the regulatory profile of PFIs on the expressions of ER isoforms and ER alpha phosphorylation, providing a new perspective for assessing endocrine disrupting effects of the emerging chemicals of concern. (C) 2021 Published by Elsevier B.V.