Exposure to the endocrine disruptor Hexachlorobenzene promotes breast tumor growth and metastasis in a HER2-positive breast cancer model

LORENA ZÁRATE; JORGE PEÑA AGUDELO; NOELIA MIRET; ALEJANDRO NICOLA CANDIA; FLORENCIA CHIAPPINI; CAROLINA PONTILLO; MARIANELA CANDOLFI; ANDREA RANDI

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias; 2021

The death rate from breast cancer has increased significantly in the last 25 years. Exposure to endocrine-disrupting chemicals, such as pesticides, has been postulated as a risk factor in this disease. We have previously demonstrated that the organochlorine Hexachlorobenzene (HCB) has stimulated breast tumor progression, favoring cell migration, invasion and angiogenesis. HCB is a weak ligand of the Aromatic Hydrocarbon Receptor (AhR), a transcription factor related to tumor and vascular development. Furthermore, we have reported that HCB acts as an endocrine disruptor in the mammary gland and uterus in different animal models. Estrogens play a fundamental role in the etiology of breast cancer, whose actions are mediated by their α and β isoform receptors. However, the role of ER-β is not entirely clear, with evidence of a reduction in proliferation and angiogenesis in ERα-positive breast cancer cell lines, while in triple-negative cells (RE-/RP-/HER2-) performs the opposite function. G-protein-coupled ER (GPR30) mediates the action of estrogens in breast tumors and cancer-associated fibroblasts, leading to tumor progression. In the present study, we have examined the action of HCB (0.03, 0.3 and 3 mg/kg body weight, bw) in a LM3 syngeneic breast cancer mouse model (ER-/PR-/HER2+). Our results indicated that HCB induces an increase in tumor weight and volume at 3 mg/kg bw (p