Involvement of LXR ligands in controlling proliferation of mammary epithelial cells

RADICE M; PECCI A; DANSEY MV; OGARA M.F

Mar del Plata

Congreso; LXIX Reunion Anual de SAIC; 2019

LXRs are transcription factors activated by cholesterol metabolites whose target genes participate in the de novo synthesis of triglycerides and cholesterol reverse transport in many tissues. Two different LXR isoforms has been described: LXRα and LXRβ. Genetic and pharmacological studies defined them as key factors connecting cellular processes such as lipid metabolism, inflammation and cellular proliferation and death. Recent evidence suggests that LXR activation and consequent intracellular cholesterol decrease have antitumoral effect. However, it was also demonstrated that LXR activation favors Warburg effect, relevant in tumor cells. In these sense, our goal was to evaluate the role of LXRs on breast cancer cell proliferation and migration. Here, we report that both LXR isoforms are expressed in ER+breast cancer (BC) cell line MCF7 and in ER- BC cells MDA-mb-231. The expression of LXR isoform was inhibited in MDA-mb-231 upon treatment with the commercial LXR agonist GW39065 (1 M) while LXR levels remained unaffected. Cell viability results assessed by MTT assays suggest that in MCF-7 cells treated with or without estradiol (10nM), GW39065 (1 M) decreases cell proliferation upon 24 h treatment. However this effect was not observed in MDA-231 cells. On the other hand, wound healing assays suggested that the LXR agonist increases MDA-231 but does not affect MCF-7 cell migration. LXR signaling would arise as a relevant pathway in controlling breast cancer cells proliferation. However, its involvement would dependent on each cellular context.