Lack of liver X receptors leads to cell proliferation in a model of mouse dorsal prostate epithelial cell

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 Lx...

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Veröffentlicht in:PloS one 2013-03, Vol.8 (3), p.e58876-e58876
Hauptverfasser: Dufour, Julie, Pommier, Aurélien, Alves, Georges, De Boussac, Hugues, Lours-Calet, Corinne, Volle, David H, Lobaccaro, Jean-Marc A, Baron, Silvère
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container_title PloS one
container_volume 8
creator Dufour, Julie
Pommier, Aurélien
Alves, Georges
De Boussac, Hugues
Lours-Calet, Corinne
Volle, David H
Lobaccaro, Jean-Marc A
Baron, Silvère
description 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.
doi_str_mv 10.1371/journal.pone.0058876
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subjects ABCA1 protein
Activation
AKT protein
Animals
Apoptosis
ATP-binding protein
Biology
Cancer
Cell culture
Cell cycle
Cell Line
Cell Proliferation
Cholesterol
Epithelial cells
Epithelial Cells - metabolism
Extracellular matrix
Fatty acids
Gene Order
Gene Targeting
Genotype
Homeostasis
Homeostasis - genetics
Hyperplasia
Kinases
Ligands
Lipid Metabolism - genetics
Liver
Liver X Receptors
Male
MAP kinase
Medicine
Mice
Mice, Knockout
Mitogen-Activated Protein Kinases - metabolism
Molecular modelling
Nutrition
Orphan Nuclear Receptors - genetics
Orphan Nuclear Receptors - metabolism
Pascal, Blaise (1623-1662)
Pathways
Pharmacology
Phosphorylation
Prostate - metabolism
Prostate cancer
Proto-Oncogene Proteins c-akt - metabolism
Receptors
Regulation
Rodents
Signal Transduction
Stromal Cells - metabolism
Studies
Survival
title Lack of liver X receptors leads to cell proliferation in a model of mouse dorsal prostate epithelial cell
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