Lack of Liver X Receptors Leads to Cell Proliferation in a Model of Mouse Dorsal Prostate Epithelial Cell |
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| Authors: | Julie Dufour Aurélien Pommier Georges Alves Hugues De Boussac Corinne Lours-Calet David H Volle Jean-Marc A Lobaccaro Silvère Baron |
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| Institution: | 1. Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement (GReD), Clermont-Ferrand, France.; 2. CNRS, UMR 6293, GReD, Aubiere, France.; 3. INSERM, UMR 1103, GReD, Aubiere, France.; 4. Centre de Recherche en Nutrition Humaine d’Auvergne, Clermont-Ferrand, France.; Nihon University School of Medicine, Japan, |
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| Abstract: | Recent studies underline the implication of Liver X Receptors (LXRs) in several prostate diseases such as benign prostatic hyperplasia (BPH) and prostate cancer. In order to understand the molecular mechanisms involved, we derived epithelial cells from dorsal prostate (MPECs) of wild type (WT) or Lxrαβ−/− mice. In the WT MPECs, our results show that LXR activation reduces proliferation and correlates with the modification of the AKT-survival pathway. Moreover, LXRs regulate lipid homeostasis with the regulation of Abca1, Abcg1 and Idol, and, in a lesser extent, Srebp1, Fas and Acc. Conversely cells derived from Lxrαβ−/− mice show a higher basal phosphorylation and consequently activation of the survival/proliferation transduction pathways AKT and MAPK. Altogether, our data point out that the cell model we developed allows deciphering the molecular mechanisms inducing the cell cycle arrest. Besides, we show that activated LXRs regulate AKT and MAPK transduction pathways and demonstrate that LXRs could be good pharmacological targets in prostate disease such as cancer. |
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