Organochlorine pesticide modulates TGF-β1/ Aryl Hydrocarbon Receptor crosstalk in vitro, and enhances hyperplasia and branching morphogenesis in mouse mammary gland

NOELIA MIRET; EVA RICO-LEO; CAROLINA PONTILLO; ELSA ZOTTA; PEDRO FERNÁNDEZ SALGUERO; ANDREA RANDI

Mérida

Congreso; XIV International Congress of Toxicology; 2016

International Union of Toxicology

Hexachlorobenzene (HCB) is one of the most widespread environmental pollutants and an endocrine disruptor in animal models. HCB is a dioxin-like compound and a ligand of the Aryl Hydrocarbon Receptor (AhR). We have demonstrated that HCB induces proliferation, migration and invasion in human breast cancer cells, as well as tumor growth and metastasis in vivo. AhR is highly expressed and constitutively active in breast cancer and its activity correlates with tumor aggressiveness. Transforming Growth Factor-β1 (TGF-β1) is critically important in mammary morphogenesis and is notoriously activated during breast cancer development. AhR and TGF-β1 converge to regulate signaling pathways such as cell proliferation, migration and apoptosis. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling pathways in mammary gland in vitro and in vivo. Mouse mammary epithelial cell line (NMuMG) and immortalized fibroblast (FGM) cells were treated with HCB (0.005, 0.05, 0.5 and 5 µM). AhR+/+ and AhR-/- mice were exposure to HCB (3 mg/kg body weight) by intraperitoneal injection four times a week for 21 days. Our results showed a biphasic effect in NMuMG cells, inducing cell migration (21%, p