caa a22 4500 475806123 CHVBK 20180406123747.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1023/A:1026544214667 doi (NATIONALLICENCE)springer-10.1023/A:1026544214667 Semenza Gregg Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA aut HIF-1: Using Two Hands to Flip the Angiogenic Switch [Elektronische Daten] [Gregg Semenza] In brain, breast, and other common human tumors there is a correlation between expression of the transcriptional activator hypoxia-inducible factor 1 (HIF-1) and tumor grade and vascularization. HIF-1 stimulates angiogenesis by activating transcription of the gene encoding vascular endothelial growth factor (VEGF). HIF-1 is a heterodimer consisting of a constitutively-expressed HIF-1β subunit and an O2- and growth factor-regulated HIF-1α subunit. Recent studies have demonstrated that HIF-1α expression is increased in tumor relative to normal tissue by two mechanisms. First, decreased intratumoral O2 concentrations provide a physiological stimulus. Second, genetic alterations that activate oncogene products or inactivate tumor suppressor gene products increase HIF-1α expression and/or HIF-1 transcriptional activity independent of the O2 concentration. Taken together, these recent data suggest that increased HIF-1 activity provides a molecular basis for VEGF-induced angiogenesis and other adaptations of cancer cells to hypoxia that are critical for establishment of a primary tumor and its progression to the lethal phenotype. Kluwer Academic Publishers, 2000 AKT nationallicence MAP kinase nationallicence p53 nationallicence phosphatidylinositol-3-kinase nationallicence PTEN nationallicence SRC nationallicence vascular endothelial growth factor nationallicence von Hippel-Lindau protein nationallicence Cancer and Metastasis Reviews Kluwer Academic Publishers 19/1-2(2000-06-01), 59-65 0167-7659 19:1-2<59 2000 19 10555 https://doi.org/10.1023/A:1026544214667 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1026544214667 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Semenza Gregg Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA aut NATIONALLICENCE 773 0- Cancer and Metastasis Reviews Kluwer Academic Publishers 19/1-2(2000-06-01), 59-65 0167-7659 19:1-2<59 2000 19 10555 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer