title: Lack of liver X receptors leads to cell proliferation in a model of mouse dorsal prostate epithelial cell.
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.
authors.affiliation: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, Clermont-Ferrand, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Dufour
authors.forename: Aurélien
authors.initials: A
authors.lastname: Pommier
authors.forename: Georges
authors.initials: G
authors.lastname: Alves
authors.forename: Hugues
authors.initials: H
authors.lastname: De Boussac
authors.forename: Corinne
authors.initials: C
authors.lastname: Lours-Calet
authors.forename: David H
authors.initials: DH
authors.lastname: Volle
authors.forename: Jean-Marc A
authors.initials: JM
authors.lastname: Lobaccaro
authors.forename: Silvère
authors.initials: S
authors.lastname: Baron
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D023061:Gene Order; D018390:Gene Targeting; D005838:Genotype; D006706:Homeostasis / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000235:genetics* / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
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