rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2000-8-8
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pubmed:abstractText |
In this study, we investigated the mechanisms responsible for the growth-inhibitory action of parathyroid hormone-related protein (PTHRP) in A10 vascular smooth muscle cells (VSMC). Fluorescence-activated cell sorting analysis of serum-stimulated VSMC treated with PTHRP or dibutyryl-cAMP (DBcAMP) demonstrated an enrichment of cells in G1 and a reduction in the S phase. Measurement of DNA synthesis in platelet-derived growth factor-stimulated VSMC treated with DBcAMP revealed that cells became refractory to growth inhibition by 12-16 h, consistent with blockade in mid-G1. cAMP treatment blunted the serum-induced rise in cyclin D1 during cell cycle progression without altering levels of the cyclin-dependent kinase cdk4 or cyclin E and its associated kinase, cdk2. Exposure of cells to PTHRP or cAMP resulted in a reduction in retinoblastoma gene product (Rb) phosphorylation. Immunoblotting of extracts from cAMP-treated cells with antibodies to cdk inhibitors revealed a striking increase in p27(kip1) abundance coincident with the G1 block. Immunoprecipitation with an anti-cyclin D1 antibody of cell lysates prepared from cAMP-treated cells followed by immunoblotting with antisera to p27(kip1) disclosed a threefold increase in p27(kip1) associated with cyclin D1 compared with lysates treated with serum alone. We conclude that PTHRP, by increasing intracellular cAMP, induces VSMC cycle arrest in mid-G1. This occurs secondary to a suppression in cyclin D1 and induction of p27(kip1) expression, which in turn inhibits Rb phosphorylation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Parathyroid Hormone-Related Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0193-1849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
E60-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10893323-Bucladesine,
pubmed-meshheading:10893323-Cell Cycle Proteins,
pubmed-meshheading:10893323-Cell Division,
pubmed-meshheading:10893323-Cell Line,
pubmed-meshheading:10893323-Cyclic AMP,
pubmed-meshheading:10893323-Cyclin-Dependent Kinase 4,
pubmed-meshheading:10893323-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:10893323-Cyclin-Dependent Kinases,
pubmed-meshheading:10893323-Cyclins,
pubmed-meshheading:10893323-Enzyme Inhibitors,
pubmed-meshheading:10893323-G1 Phase,
pubmed-meshheading:10893323-Microtubule-Associated Proteins,
pubmed-meshheading:10893323-Muscle, Smooth, Vascular,
pubmed-meshheading:10893323-Parathyroid Hormone-Related Protein,
pubmed-meshheading:10893323-Proteins,
pubmed-meshheading:10893323-Proto-Oncogene Proteins,
pubmed-meshheading:10893323-Tumor Suppressor Proteins
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pubmed:year |
2000
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pubmed:articleTitle |
Parathyroid hormone-related protein induces G1 phase growth arrest of vascular smooth muscle cells.
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pubmed:affiliation |
Departments of Medicine and Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio 45267, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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