Environmental exposure and mammary tumors: the pesticides action on LM3 murine breast cancer cells

Lorena V. Zárate¹, Alejandro J. Nicola Candia², Noelia V. Miret¹, Antonela S. Asad², Carolina A. Pontillo¹, Leandro J . Ceballos¹, Florencia A. Chiappini¹, Marianela Candolfi², Andrea S. Randi¹

Epidemiological studies have shown that pesticide exposure is associated with an increased risk of breast cancer, while the organochlorines body burden may influence the development of a specific subtype of breast tumor. Human epidermal growth factor receptor 2 (HER2) is associated with poorer survival, while the role of the estrogen receptor β (ERβ) in breast cancer is not entirely clear. The organochlorine pesticide hexachlorobenzene (HCB) is a weak ligand for the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor related to vascular and tumor development. Stem cells are of great interest for their ability to originate, maintain and expand tumors, as well as to cause metastasis and recurrences. Our aim was to investigate the HCB action (0.005, 0.05, 0.5 and 5 μM) on the expression of proangiogenic factors, cell viability, proliferation, migration and mammospheres development in murine breast cancer cells LM3 (ERα-/HER2+). Our results indicated that HCB increased cell viability, proliferation and migration at 0.05 and 5 μM, through an AhR-dependent mechanism (p <0.001). In addition, HCB induced the expression of VEGF and COX-2 at 0.05 and 0.5 μM (p <0.05) and, in all the doses tested, the pesticide stimulated the development of mammospheres while reducing the ERβ expression (p <0.001). These results suggest that HCB promotes a dedifferentiated, proliferative and proangiogenic environment, contributing to tumor progression in a HER2+ breast cancer model.