Liver X receptor: effect of two cholestenoic acid analogues on mouse mammary epithelial cells.

GRINMAN, D; DANSEY MV; NAVLESI D; SAMAJA GA; ALVAREZ, LD; VELEIRO, AS; BURTON, G.; PECCI, A.

Puerto Varas

Congreso; XII PABMB Congress.; 2013

SAIB

Liver X receptors (α and β) are oxysterols-activated transcription factors that belong to the nuclear hormone receptor superfamily. . LXRs are involved in many physiological functions such as lipid de novo synthesis and excretion, cell proliferation and apoptosis. In mammary gland, LXRs not only control lipid levels during lactation but also has antiproliferative and proapoptotic effects. Our aim was to evaluate the role of LXR activation on a mouse mammary epithelial cell line (HC11) and to assay in vitro activity of two novel cholestenoic acid analogues: 27-nor and 27-nor -Δ24 3-hydroxy-5-cholestenoic acids. HC11 cells are broadly used as a mammary cell differentiation and apoptosis model. EGF protects these cells from apoptosis when cultured in serum free medium mainly throughout AKT survival pathway activation. Both LXRα/β are expressed in all HC11 differentiation stages. The cholestenoic acid derivatives showed antagonistic activity when co-incubated with the LXR agonist GW3965 in cells transfected with a luciferase reporter vector responding to LXR. Moreover, these compounds also inhibited GW3965 mediated expression induction of several genes involved in lipogenesis and cholesterol efflux. Surprisingly, preliminary results suggest that these analogues decrease EGF mediated AKT activation on HC11 cells, becoming important tools to understand LXRs participation on mammary gland milk lipid production, cell proliferation and death.