CHLORPYRIFOS PROMOTES CANCER STEM CELL SELECTION AND REGULATES THE EXPRESSION OF GENES LINKED TO ANTIESTROGEN THERAPY RESISTANCE IN BREAST CANCER

LASAGNA MARIANELA; ZAPPIA C. DANIEL; MARDIROSIAN MARIANA NOELIA; MARTÍN GABRIELA; MIRET NOELIA V; RANDI ANDREA; NUÑEZ MARIEL; COCCA CLAUDIA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

SAIC SAB AAFE AACYTAL

Loss of Estrogen Receptor α (ERα) expression is critical for breast cancer progression and considered to be one of the mechanisms of resistance to endocrine therapy. It is postulated that histone deacetylase 1 (HDAC1) interacts with ERα and suppresses ERα transcriptional activity. The organophosphorus chlorpyrifos (CPF) is currently classified as an Endocrine Disruptor (ED), as it can simulate hormone actions both in vitro and in vivo. EDs have been associated with endocrine therapy resistance. In this study, we investigated whether CPF can induce mechanisms associated with resistance to antiestrogen therapy such as the proliferation of cancer stem cells (CSC) and/or HDAC1 and ERα modulation. Our experiments were performed using MCF-7 cell line (ERα+) or MDA-MB231 and MCF10A (ERα-) cell lines. We analyzed if CPF (0.05 and 50 μM) induces CSC proliferation by mammosphere (MS1) assay and/or ERα, HDAC1 and the co-repressor SMRT expression in monolayer cells and MS1 by RT-qPCR. To elucidate the participation of ERα in the modulation of HDAC1 expression, we evaluated comparatively, the expression of this enzyme in MDA-MB-231 and MCF-10A. CPF at 0.05 μM increases the subpopulation of CSC derived from MCF-7 cells (p