Data from: Molecular mechanisms of polybrominated diphenyl ethers (BDE-47, -100 and -153) in human breast cancer cells and patient-derived xenografts

Polybrominated Diphenyl Ethers (PBDEs) have been used as flame retardants
in household materials. Their environmental persistence has led to
continuous human exposure and significant tissue levels. Three PBDE
congeners (BDE-47, -100, and -153) have been frequently detected in human
serum. While these compounds appear to possess endocrine disrupting
activity, studies are largely missing to determine the biological
mechanisms of PBDEs in breast cancer cells. Here, we assessed PBDE
bio-activities with three complementary strategies: receptor
binding/activity assays; non-biased RNA-sequencing analysis using an
estrogen-dependent breast cancer cell line MCF-7aroERE; and in vivo
assessments using patient-derived xenograft (PDX) models of human breast
cancer. According to the results from in vitro experiments, the PBDE
congeners regulate distinct nuclear receptor signaling pathways. BDE-47
acts as a weak agonist of both estrogen receptor α (ERα) and
estrogen-related receptor α (ERRα); it could stimulate proliferation of
MCF-7aroERE and induced expression of ER-regulated genes (including cell
cycle genes). BDE-153 was found to act as a weak antagonist of ERα.
BDE-100 could act as 1) an agonist of aryl hydrocarbon receptor (AhR),
inducing expression of CYP1A1 and CYP1B1 and 2) as a very weak
agonist/antagonist of ERα. In vivo, a mixture of the three congeners with
ratios detected in human serum was tested in an ER+ PDX model. The mixture
exhibited estrogenic activity through apoptosis/cell cycle regulation and
increased the expression of a proliferation marker, Ki-67. These results
advance our understanding of the mechanisms of PBDE exposure in breast
cancer cells.