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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-1-6
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-23
pubmed:dateRevised
2008-11-21
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
pubmed:year
2000
pubmed:articleTitle
Regulation of vascular endothelial growth factor expression by insulin-like growth factor-I in endometrial adenocarcinoma cells.
pubmed:affiliation
Service d'Oncologie et d'Endocrinologie Moléculaire (C.H.U. Besançon and IETG) and C.R.I 96.01, Besançon, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't