Source:http://linkedlifedata.com/resource/pubmed/id/10585594
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2000-1-6
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pubmed:abstractText |
Angiogenesis is crucial for tumor growth and dissemination. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that promotes endothelial cell proliferation and chemotaxis. VEGF occurs as 5 isoforms, as a result of an alternatively spliced transcript that originates from one gene, of which the 2 majors are the VEGF 121 and 165 isoforms. Our aim was firstly to determine the role of Insulin-like Growth Factor-I (IGF-I) in the regulation of VEGF expression in endometrial adenocarcinoma cells and then the mechanism by which this regulation occurs. IGF-I treatment of HEC-1A cells provoked an increase of VEGF mRNA expression that peaked at 48 hr with a 165 isoform mRNA more abundant than the 121 isoform. The IGF-I action was confirmed at the protein level, whose concentration was increased in the conditioned media. In experiments using transient transfection of VEGF promoter-luciferase constructs, the IGF-I failed to increase the activity of the VEGF promoter after a 24-hr period of IGF-I treatment, while the addition of Actinomycin D showed an increase of the VEGF mRNA half-life. Most interestingly, Northern blot analysis showed a different stability of the 2 major VEGF isoform mRNAs (VEGF 121 and 165), of which the 121 isoform was more stable than the 165 isoform. The IGF-I treatment prolonged the half-life of both of the VEGF isoform mRNAs. Our results suggest that IGF-I regulates VEGF expression in endometrial adenocarcinoma cells at the post-transcriptional level by enhancing the stabilization of the 2 major VEGF isoform mRNAs (VEGF(121) and VEGF(165)). In addition to its proliferative functions, IGF-I induces VEGF expression and participates in the maintenance of an angiogenic phenotype.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2000 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
85
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
117-23
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10585594-Adenocarcinoma,
pubmed-meshheading:10585594-Alternative Splicing,
pubmed-meshheading:10585594-Blotting, Northern,
pubmed-meshheading:10585594-Dactinomycin,
pubmed-meshheading:10585594-Dose-Response Relationship, Drug,
pubmed-meshheading:10585594-Endometrial Neoplasms,
pubmed-meshheading:10585594-Endothelial Growth Factors,
pubmed-meshheading:10585594-Female,
pubmed-meshheading:10585594-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10585594-Genes, Reporter,
pubmed-meshheading:10585594-Humans,
pubmed-meshheading:10585594-Insulin-Like Growth Factor I,
pubmed-meshheading:10585594-Lymphokines,
pubmed-meshheading:10585594-Promoter Regions, Genetic,
pubmed-meshheading:10585594-Protein Isoforms,
pubmed-meshheading:10585594-RNA, Messenger,
pubmed-meshheading:10585594-RNA Stability,
pubmed-meshheading:10585594-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10585594-Time Factors,
pubmed-meshheading:10585594-Transfection,
pubmed-meshheading:10585594-Tumor Cells, Cultured,
pubmed-meshheading:10585594-Vascular Endothelial Growth Factor A,
pubmed-meshheading:10585594-Vascular Endothelial Growth Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Regulation of vascular endothelial growth factor expression by insulin-like growth factor-I in endometrial adenocarcinoma cells.
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pubmed:affiliation |
Service d'Oncologie et d'Endocrinologie Moléculaire (C.H.U. Besançon and IETG) and C.R.I 96.01, Besançon, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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