|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
17
|
|
pubmed:dateCreated |
2004-4-19
|
|
pubmed:abstractText |
Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) following exposure to PPARgamma-specific ligands resulted in growth inhibition in various carcinoma cell lines. Our aim was to elucidate the pathway of PPARgamma2 activation-mediated modulation of cyclin D1 transcription in mouse hepatocytes. To address this we utilized stable control and PPARgamma hepatocyte cell lines created via retroviral overexpression utilizing AML-12 hepatocytes. Addition of PPARgamma ligand troglitazone (TZD) activated PPARgamma2 in proliferating hepatocytes and resulted in growth arrest accompanied by a down-regulation of proliferating cell nuclear antigen, cyclin D1, and beta-catenin expression. Furthermore activation of PPARgamma2 attenuated cyclin D1 promoter activity indicating a transcriptional regulation of cyclin D1. Since beta-catenin plays a pivotal role in regulating cyclin D1 transcription, we studied whether PPARgamma2-mediated inhibition of cyclin D1 transcription involved beta-catenin. Interestingly overexpression of either wild-type or S37A mutant beta-catenin was unable to rescue PPARgamma2-mediated suppression of cyclin D1 transcription, whereas overexpression of cAMP-response element-binding protein (CREB) was capable of antagonizing this inhibitory effect of PPARgamma2. Additionally pretreatment with okadaic acid antagonized PPARgamma2-mediated inhibition of cyclin D1 transcription without any effect on beta-catenin expression. These studies also showed a TZD-mediated inhibition of total and phospho-CREB(Ser133) levels, CREB promoter activity, and cAMP-response element-mediated transcription in PPARgamma hepatocytes. Pretreatment of PPARgamma hepatocytes with okadaic acid, however, maintained higher total and phospho-CREB(Ser133) levels in the presence of TZD. These results indicated that PPARgamma2 activation inhibited cyclin D1 transcription in hepatocytes via CREB-dependent and beta-catenin-independent pathways.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chromans,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Okadaic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/troglitazone
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
23
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
16927-38
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:14764597-Animals,
pubmed-meshheading:14764597-Blotting, Western,
pubmed-meshheading:14764597-Cell Division,
pubmed-meshheading:14764597-Cell Line,
pubmed-meshheading:14764597-Chromans,
pubmed-meshheading:14764597-Cyclic AMP,
pubmed-meshheading:14764597-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:14764597-Cyclin D1,
pubmed-meshheading:14764597-Cytoskeletal Proteins,
pubmed-meshheading:14764597-Enzyme Activation,
pubmed-meshheading:14764597-Enzyme Inhibitors,
pubmed-meshheading:14764597-Genes, Reporter,
pubmed-meshheading:14764597-Hepatocytes,
pubmed-meshheading:14764597-Humans,
pubmed-meshheading:14764597-Hypoglycemic Agents,
pubmed-meshheading:14764597-Ligands,
pubmed-meshheading:14764597-Liver,
pubmed-meshheading:14764597-Luciferases,
pubmed-meshheading:14764597-Mice,
pubmed-meshheading:14764597-Mutation,
pubmed-meshheading:14764597-Okadaic Acid,
pubmed-meshheading:14764597-Plasmids,
pubmed-meshheading:14764597-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:14764597-Serine,
pubmed-meshheading:14764597-Thiazolidinediones,
pubmed-meshheading:14764597-Trans-Activators,
pubmed-meshheading:14764597-Transcription, Genetic,
pubmed-meshheading:14764597-Transcription Factors,
pubmed-meshheading:14764597-Transfection,
pubmed-meshheading:14764597-beta Catenin
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Peroxisome proliferator-activated receptor gamma activation modulates cyclin D1 transcription via beta-catenin-independent and cAMP-response element-binding protein-dependent pathways in mouse hepatocytes.
|
|
pubmed:affiliation |
Division of Molecular Cardiology, The Texas A&M University System Health Science Center, College of Medicine, Temple, Texas 76504, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
