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- W2068176952 abstract "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 (VEGF121 and VEGF165). In addition to its proliferative functions, IGF-I induces VEGF expression and participates in the maintenance of an angiogenic phenotype. Int. J. Cancer 85:117–123, 2000. © 2000 Wiley-Liss, Inc." @default.
- W2068176952 created "2016-06-24" @default.
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- W2068176952 date "2000-01-01" @default.
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- W2068176952 title "Regulation of vascular endothelial growth factor expression by insulin-like growth factor-I in endometrial adenocarcinoma cells" @default.
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- W2068176952 doi "https://doi.org/10.1002/(sici)1097-0215(20000101)85:1<117::aid-ijc21>3.0.co;2-x" @default.
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