caa a22 4500 475806018 CHVBK 20180406123747.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1023/A:1026506011458 doi (NATIONALLICENCE)springer-10.1023/A:1026506011458 MAP Kinases and Hypoxia in the Control of VEGF Expression [Elektronische Daten] [Edurne Berra, Gilles Pagès, Jacques Pouysségur] Vascular endothelial growth factor (VEGF), a potent cytokine secreted by virtually all cells plays a key role in tumor angiogenesis. Disruption of one VEGF allele in mice has revealed a dramatic lethal effect in early embryogenesis, suggesting a very tight regulation of this gene. This commentary reviews the mechanisms whereby VEGF mRNA is controlled within the tumor environment by hypoxia and the MAP kinase signaling cascades. Using hamster fibroblasts as a cellular model, we demonstrated that the Ras-mediated activation of p42/p44 MAP kinases exerts a prominent action at the transcriptional level. In normoxic conditions, p42/p44 MAPKs activate the VEGF promoter at the proximal (−88/−66) region where Sp1/AP-2 transcriptional factor complexes are recruited. At low O2 tension, the stabilized and nuclear hypoxia inducible factor-1α (HIF-1α) is directly phosphorylated by p42/p44 MAPKs, an action which enhances HIF-1-dependent transcriptional activition of VEGF. In addition, MAPKs activated under various cellular stresses (p38MAPK and JNK), contribute to the increased expression of this angiogenic growth and survival factor by stabilizing the VEGF mRNA. Kluwer Academic Publishers, 2000 VEGF nationallicence MAP kinases nationallicence hypoxia nationallicence angiogenesis nationallicence growth control nationallicence Berra Edurne Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, Nice, France aut Pagès Gilles Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, Nice, France aut Pouysségur Jacques Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, Nice, France aut Cancer and Metastasis Reviews Kluwer Academic Publishers 19/1-2(2000-06-01), 139-145 0167-7659 19:1-2<139 2000 19 10555 https://doi.org/10.1023/A:1026506011458 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1026506011458 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Berra Edurne Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, Nice, France aut NATIONALLICENCE 700 1- Pagès Gilles Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, Nice, France aut NATIONALLICENCE 700 1- Pouysségur Jacques Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, Nice, France aut NATIONALLICENCE 773 0- Cancer and Metastasis Reviews Kluwer Academic Publishers 19/1-2(2000-06-01), 139-145 0167-7659 19:1-2<139 2000 19 10555 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer