Sp1 is involved in Akt-mediated induction of VEGF expression through an HIF-1-independent mechanism.
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| Title: | Sp1 is involved in Akt-mediated induction of VEGF expression through an HIF-1-independent mechanism. |
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| Authors: | Pore, Nabendu, Liu, Shuang, Shu, Hui-Kuo, Li, Bin, Haas-Kogan, Daphne, Stokoe, David, Milanini-Mongiat, Julie, Pages, Gilles, O'Rourke, Donald M, Bernhard, Eric, Maity, Amit |
| Contributors: | Dept. of Radiation Oncology, University of Pennsylvania, University of Pennsylvania, Dept. of Radiation Oncology, UCSF, University of California San Francisco (UC San Francisco), University of California (UC)-University of California (UC), Cancer Research Institute, UCSF, Institut de signalisation, biologie du développement et cancer - Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Dept. of Neurosurgery, University of Pennsylvania |
| Source: | EISSN: 1939-4586 ; Molecular Biology of the Cell ; https://hal.science/hal-00323612 ; Molecular Biology of the Cell, 2004, 15 (11), pp.4841-53. ⟨10.1091/mbc.E04-05-0374⟩ |
| Publisher Information: | CCSD American Society for Cell Biology |
| Publication Year: | 2004 |
| Collection: | HAL Université Côte d'Azur |
| Subject Terms: | MESH: Chromatography, Liquid, MESH: Diffusion, MESH: Exploratory Behavior, MESH: Feeding Behavior, MESH: Homing Behavior, MESH: Sodium Chloride, MESH: Soil, MESH: Thailand, MESH: DNA-Binding Proteins, MESH: Humans, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, MESH: Hydrocarbons, Aromatic, MESH: Nuclear Proteins, MESH: Promoter Regions (Genetics), MESH: Sp1 Transcription Factor, MESH: Transcription Factors, MESH: Transcription, Genetic, MESH: Vascular Endothelial Growth Factors, MESH: 1-Phosphatidylinositol 3-Kinase, MESH: Adenoviridae, MESH: Alkaline Phosphatase, MESH: Anoxia, MESH: Ketones, MESH: Base Sequence, MESH: Binding Sites, MESH: Blotting |
| Description: | International audience ; Increased expression of vascular endothelial growth factor (VEGF) contributes to the growth of many tumors by increasing angiogenesis. Although hypoxia is a potent inducer of VEGF, we previously showed that epidermal growth factor receptor amplification and loss of PTEN, both of which can increase phosphatidylinositol-3-kinase (PI3K) activity, increase VEGF expression. Using both adenoviral vectors and a cell line permanently expressing constitutively active myristoylated Akt (myrAkt), we show that activation of Akt, which is downstream of PI3K, increases VEGF expression in vitro and increases angiogenesis in a Matrigel plug assay. Transient transfection experiments using reporter constructs containing the VEGF promoter showed that up-regulation of VEGF by Akt is mediated through Sp1 binding sites located in the proximal promoter. Small interfering RNA directed against Sp1 prevented the induction of VEGF mRNA in response to myrAkt but not to hypoxia. Expression of myrAkt is associated with increased phosphorylation of Sp1 and its increased binding to a probe corresponding to the -88/-66 promoter region. In conclusion, our results indicate that Sp1 is required for transactivation of the VEGF by Akt. Others have proposed that the PI3K/Akt pathway can increase VEGF expression via the hypoxia-inducible factor 1 (HIF-1); however, our results suggest an alternative mechanism can also operate. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/15342781; PUBMED: 15342781; PUBMEDCENTRAL: PMC524732 |
| DOI: | 10.1091/mbc.E04-05-0374 |
| Availability: | https://hal.science/hal-00323612 https://doi.org/10.1091/mbc.E04-05-0374 |
| Accession Number: | edsbas.49CECC3F |
| Database: | BASE |
Nájsť tento článok vo Web of Science | Abstract: | International audience ; Increased expression of vascular endothelial growth factor (VEGF) contributes to the growth of many tumors by increasing angiogenesis. Although hypoxia is a potent inducer of VEGF, we previously showed that epidermal growth factor receptor amplification and loss of PTEN, both of which can increase phosphatidylinositol-3-kinase (PI3K) activity, increase VEGF expression. Using both adenoviral vectors and a cell line permanently expressing constitutively active myristoylated Akt (myrAkt), we show that activation of Akt, which is downstream of PI3K, increases VEGF expression in vitro and increases angiogenesis in a Matrigel plug assay. Transient transfection experiments using reporter constructs containing the VEGF promoter showed that up-regulation of VEGF by Akt is mediated through Sp1 binding sites located in the proximal promoter. Small interfering RNA directed against Sp1 prevented the induction of VEGF mRNA in response to myrAkt but not to hypoxia. Expression of myrAkt is associated with increased phosphorylation of Sp1 and its increased binding to a probe corresponding to the -88/-66 promoter region. In conclusion, our results indicate that Sp1 is required for transactivation of the VEGF by Akt. Others have proposed that the PI3K/Akt pathway can increase VEGF expression via the hypoxia-inducible factor 1 (HIF-1); however, our results suggest an alternative mechanism can also operate. |
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| DOI: | 10.1091/mbc.E04-05-0374 |