PESTICIDE EXPOSURE PROMOTES ESTROGEN RECEPTOR EXPRESSION DYSREGULATION AND IMMUNOTOXICITY IN HER2-POSITIVE BREAST CANCER MODEL IN MICE

ZÁRATE LV; PEÑA AGUDELO JA; MIRET NV; NICOLA CANDIA AJ; CHIAPPINI FA; PONTILLO CA; CANDOLFI M; RANDI AS

Mar del Plata

Congreso; VIII SETAC Arg 2022; 2022

Exposure to environmental pollutants, such as pesticides, has been established as a riskfactor for breast tumors, the leading cause of death by cancer in women worldwide. We havepreviously demonstrated that the organochlorine Hexachlorobenzene (HCB) facilitatesbreast cancer progression, stimulating cell migration, invasion and angiogenesis. HCB is aweak ligand for the Aryl Hydrocarbon Receptor (AhR), a transcription factor related to tumorand vascular development, and an important regulator of T cell differentiation. In addition, wehave reported that HCB acts as an endocrine disruptor in the mammary gland and uterus ina variety of animal models. This could affect the expression of the different types of estrogenreceptors (ER), such as ER-β and G protein estrogen receptor (GPER), which are related tobreast tumor progression. In the present study, we examined the action of the exposure tothe HCB (0.03, 0.3 and 3 mg/kg body weight, bw) in LM3 tumors, a syngeneic mouse modelof HER+ breast cancer (ER-/PR-/HER2+) for 30 days. In addition, we evaluated the effect ofHCB (0.005; 0.05; 0.5 and 5 μM) in the LM3 cell line for 24 h. We found that HCB inducesan increase in tumor volume at all dosis tested (p