From the Cover: Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Decreased p-β-Cateninser675 Expression and Its Interaction With E-Cadherin in the Mammary Glands of Lactating Rats

Abstract

Proper mammary gland development and function require precise hormonal regulation and bidirectional cross talk between cells provided by means of paracrine factors as well as intercellular junctions; exposure to environmental endocrine disruptors can disturb these processes. Exposure to one such family of chemicals, the brominated flame retardants (BFRs), is ubiquitous. Here, we tested the hypothesis that BFR exposures disrupt signaling pathways and intercellular junctions that control mammary gland development. Before mating, during pregnancy and throughout lactation, female Sprague-Dawley rats were fed diets containing that BFR mixture based on house dust, delivering nominal exposures of BFR of 0 (control), 0.06, 20, or 60 mg/kg/d. Dams were euthanized and mammary glands collected on postnatal day 21. BFR exposure had no significant effects on mammary gland/body weight ratios or the levels of proteins involved in milk synthesis, epithelial-mesenchymal transition, cell-cell interactions, or hormone signalling. However, BFR exposure (0.06 mg/kg/d) down-regulated phospho-ser675 β-catenin (p-β-catSer675) levels in the absence of any effect on total β-catenin levels. Levels of p-CREB were also down-regulated, suggesting that PKA inhibition plays a role. p-β-catSer675 co-localized with β-catenin at the mammary epithelial cell membrane, and its expression was decreased in animals from the 0.06 and 20 mg/kg/d BFR treatment groups. Although β-Catenin signaling was not affected by BFR exposure, the interaction between p-β-catSer675 and E-cadherin was significantly reduced. Together, our results demonstrate that exposure to an environmentally relevant mixture of BFR during pregnancy and lactation decreases p-β-catser675 at cell adhesion sites, likely in a PKA-dependant manner, altering mammary gland signaling.

SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via β-catenin activation

“…In breast cancer cell lines, β-catenin is mainly localized on the cell membrane of MCF-7 cells, while in SKBR3 cells, it is mainly localized in the cytoplasm and nucleus [ 38 ]. Cell membrane expression of pSer675-β-catenin was also observed in liver cancer cells and rat mammary gland epithelial cells [ 39 , 40 ]. We are also concerned about the result of a study showing that the expression of downstream target genes of β-catenin is not completely dependent on nuclear β-catenin [ 36 ].…”

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food

“…Several studies were identified in which the experimental animals were exposed to PBDEs together with other BFRs and/or other POPs (Allais et al., 2020 ; Berger et al., 2014 ; Berntsen et al., 2021 ; Dianati et al., 2017 ; Ernest et al., 2012 ; Gouesse et al., 2021 ; Hansen et al., 2019 ; Johanson et al., 2020 ; Khezri et al., 2017 ; Lefevre et al., 2016 ; Mailloux et al., 2014 , 2015 ; Myhre et al., 2021 ; Tung et al., 2016 , 2017 ). The CONTAM Panel did not consider these studies informative for the hazard characterisation of PBDEs and thus these studies were not considered in this Opinion.…”

Update of the risk assessment of hexabromocyclododecanes (HBCDDs) in food

“…Several studies were identified in which the animals were exposed to HBCDDs together with other BFRs and/or other POPs (Ernest et al, 2012;Berger et al, 2014;Lefevre et al, 2016;Dianati et al, 2017;Tung et al, 2016Tung et al, , 2017Allais et al, 2020). The CONTAM Panel did not consider these studies informative for the hazard characterisation of HBCDDs and thus were not considered in this Opinion.…”