Translational regulation of vascular permeability factor by eukaryotic initiation factor 4E: Implications for tumor angiogenesis
Open Access
- 15 March 1996
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 65 (6), 785-790
- https://doi.org/10.1002/(sici)1097-0215(19960315)65:6<785::aid-ijc14>3.0.co;2-3
Abstract
Studies aimed at elucidating the function of the protein synthesis factor eukaryotic initiation factor 4E (elF‐4E) have demonstrated that overexpression of this protein results in marked cell phenotypic and proliferative changes, including neoplastic transformation of cells. These data suggest that elF‐4E may somehow participate in the development and progression of tumors in vivo. In order to determine how elF‐4E exerts its transforming effects, we examined vascular permeability factor (VPF) levels in cells transfected with an elF‐4E vector. Cells overexpressing elF‐4E showed an increase in intracellular, and an average 130‐fold increase in secreted VPF protein levels (CHO 0.13 ± 0.12 ng/ml; CHO‐4E 20.5 ± 12.5 ng/ml) over control cells. HUVEC growth induction revealed these VPF levels to be biologically active. Northern analysis revealed no difference in VPF transcript between the 2 cell lines. Polysome analysis showed that the VPF message in elF‐4E‐transfected cells was associated with the heavy polysomal regions, whereas the VPF message was associated with light polysomes in control cells. These data strongly suggest that enhanced VPF expression is achieved through translational regulation rather than transcriptional regulation in cells overexpressing elF‐4E. This indicates that elF‐4E‐induced VPF expression may be an important factor in some forms of tumor angiogenesis and development.Keywords
This publication has 13 references indexed in Scilit:
- Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stabilityFEBS Letters, 1995
- Hypoxia-induced Transcriptional Activation and Increased mRNA Stability of Vascular Endothelial Growth Factor in C6 Glioma CellsJournal of Biological Chemistry, 1995
- Elevated levels of eukaryotic translation initiation factor eIF-4E, mRNA in a broad spectrum of transformed cell linesCancer Letters, 1995
- The proto‐oncogene/translation factor eIF4E: A survey of its expression in breast carcinomasInternational Journal of Cancer, 1995
- Hypoxia and platelet‐derived growth factor‐BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cellsFEBS Letters, 1995
- Expression of initiation factor genes in mammalian cellsBiochimie, 1994
- Regulation of translation and cell growth by eIF-4EBiochimie, 1994
- Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivoNature, 1993
- Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.JCI Insight, 1993
- Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors.Molecular Biology of the Cell, 1992