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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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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0058876</identifier><identifier>PMID: 23554947</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2013-03, Vol.8 (3), p.e58876-e58876</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Dufour et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>ABCA1 protein</subject><subject>Activation</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>ATP-binding protein</subject><subject>Biology</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell Line</subject><subject>Cell Proliferation</subject><subject>Cholesterol</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - metabolism</subject><subject>Extracellular matrix</subject><subject>Fatty acids</subject><subject>Gene Order</subject><subject>Gene Targeting</subject><subject>Genotype</subject><subject>Homeostasis</subject><subject>Homeostasis - genetics</subject><subject>Hyperplasia</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Lipid Metabolism - genetics</subject><subject>Liver</subject><subject>Liver X Receptors</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Molecular modelling</subject><subject>Nutrition</subject><subject>Orphan Nuclear Receptors - genetics</subject><subject>Orphan Nuclear Receptors - metabolism</subject><subject>Pascal, Blaise (1623-1662)</subject><subject>Pathways</subject><subject>Pharmacology</subject><subject>Phosphorylation</subject><subject>Prostate - metabolism</subject><subject>Prostate cancer</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors</subject><subject>Regulation</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Stromal Cells - metabolism</subject><subject>Studies</subject><subject>Survival</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7jr6D0QDgujFjEmTtumNsCx-DAws-IV3IU1PZrJmmm6SLvrvTXe6y1T2QgptOX3eN82bc7LsOcErQivy7tINvpN21bsOVhgXnFflg-yU1DRfljmmD4_eT7InIVwmiPKyfJyd5LQoWM2q08xspPqFnEbWXINHP5EHBX10PiALsg0oOqTAWtR7Z40GL6NxHTIdkmjvWrCjdu-GAKhNInkDhigjIOhN3IE1qTY6PM0eaWkDPJuei-z7xw_fzj8vNxef1udnm6Uq6zymO68IJjnJdd3UlS6wypuqbLkiuipVoXTJWIFZJSvZaqalbDhhuGqgJqUEQhfZy4Nvb10QU0pBEEoxrzmti0SsD0Tr5KXovdlL_0c4acRNwfmtkD4aZUHgvKiBqIYxzhjNmwY4IRVlVJFGNqRNXu-n1YZmD62CLnppZ6bzL53Zia27FrSoizxZLbI3k4F3VwOEKPYmjHnJDlKs6b9zlk6N1zShr_5B79_dRG1l2oDptEvrqtFUnLGKU5zSHanVPVS6WtgblVpKm1SfCd7OBImJ8Dtu5RCCWH_98v_sxY85-_qI3YG0cRecHcY2C3OQHUCVGix40HchEyzGibhNQ4wTIaaJSLIXxwd0J7odAfoX3NYFmA</recordid><startdate>20130312</startdate><enddate>20130312</enddate><creator>Dufour, Julie</creator><creator>Pommier, Aurélien</creator><creator>Alves, Georges</creator><creator>De Boussac, Hugues</creator><creator>Lours-Calet, Corinne</creator><creator>Volle, David H</creator><creator>Lobaccaro, Jean-Marc A</creator><creator>Baron, Silvère</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130312</creationdate><title>Lack of liver X receptors leads to cell proliferation in a model of mouse dorsal prostate epithelial cell</title><author>Dufour, Julie ; Pommier, Aurélien ; Alves, Georges ; De Boussac, Hugues ; Lours-Calet, Corinne ; Volle, David H ; Lobaccaro, Jean-Marc A ; Baron, Silvère</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-c687101212f9b97f50c2b76d8c1f76c5cf6445047a7adf4faab81407be916ae13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>ABCA1 protein</topic><topic>Activation</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>ATP-binding protein</topic><topic>Biology</topic><topic>Cancer</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cell Line</topic><topic>Cell Proliferation</topic><topic>Cholesterol</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - metabolism</topic><topic>Extracellular matrix</topic><topic>Fatty acids</topic><topic>Gene Order</topic><topic>Gene Targeting</topic><topic>Genotype</topic><topic>Homeostasis</topic><topic>Homeostasis - genetics</topic><topic>Hyperplasia</topic><topic>Kinases</topic><topic>Ligands</topic><topic>Lipid Metabolism - genetics</topic><topic>Liver</topic><topic>Liver X Receptors</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Molecular modelling</topic><topic>Nutrition</topic><topic>Orphan Nuclear Receptors - genetics</topic><topic>Orphan Nuclear Receptors - metabolism</topic><topic>Pascal, Blaise (1623-1662)</topic><topic>Pathways</topic><topic>Pharmacology</topic><topic>Phosphorylation</topic><topic>Prostate - metabolism</topic><topic>Prostate cancer</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptors</topic><topic>Regulation</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Stromal Cells - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23554947</pmid><doi>10.1371/journal.pone.0058876</doi><tpages>e58876</tpages><oa>free_for_read</oa></addata></record> |
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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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