LXR activation impairs estradiol-dependent proliferation in human breast cancer cells through downregulation of gene expression associated with DNA replication and cell cycle progression

OLSZANOWSKI, E.; OGARA, M.F.; NACHT, ANA SILVINA; RODRÍGUEZ SEGUÍ, S.A.; VICENT, GUILLERMO P.; PECCI, A.

Mar del Plata

Congreso; Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2022

Sociedad Argentina de Investigación Clínica (SAIC)

Liver X Receptors (LXRs) belong to the nuclear receptors superfamily of ligand activated transcription factors, whose endogenous agonists are the oxysterols. They play a key role in the regulation of the cholesterol homeostasis, induce the de novo synthesis of triacylglycerides, and counteract pro-inflammatory effects. LXRs are also known to compromise cell proliferation in several cancer models.However, their role in breast cancer (BC) has not been studied in depth and reports are, in fact,contradictory. Here we examined the potential involvement of LXRs in BC cells with special emphasis on their possible crosstalk with the Estrogen Receptor alpha (ERɑ). To address this objective, we performed colony formation (CFA) and propidium iodide staining assays in MCF-7 cells treated with or without Estradiol (E2) and the LXR agonist, GW3965. Our results showed that GW3965 impared the cell proliferation capacity induced by E2 (CFA: #colonies, Mean±SD: E2 208.7±25.7; E2+GW3965 131.3±23.7, n=3, padj