Genetic modulation of hypoxia induced gene expression and angiogenesis: Relevance to brain tumors

Frontiers in Bioscience

Volumn , Issue 4, 2003, Pages

  Brat, Daniel J ^a,b   Kaur, Balveen ^a   Van Meir, Erwin G ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b EMORY UNIVERSITY HOSPITAL   (United States)

Author keywords

Angiogenesis; Astrocytoma; Genetics; Glioblastoma Multiforme; HIF 1; Hypoxia; Review

Indexed keywords

BASIC FIBROBLAST GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; HYPOXIA INDUCIBLE FACTOR 1; OXYGEN; PHOSPHATIDYLINOSITOL 3 KINASE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN KINASE B; PROTEIN P16; PROTEIN P53; PTEN PROTEIN; THROMBOSPONDIN 1; VASCULOTROPIN;

ANGIOGENESIS; ASTROCYTOMA; BRAIN TUMOR; CARCINOGENESIS; CHROMOSOME 10; CHROMOSOME LOSS; DRUG DESIGN; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE STRUCTURE; GENE TARGETING; GENETIC TRANSCRIPTION; HEMANGIOBLASTOMA; HISTOPATHOLOGY; HUMAN; HYPOXIA; NONHUMAN; ONCOGENE; PHENOTYPE; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE; VON HIPPEL LINDAU DISEASE; ANIMAL; ANOXIA; GENETICS; NEOVASCULARIZATION (PATHOLOGY); PATHOPHYSIOLOGY; VASCULARIZATION;

ANIMALS; ANOXIA; BRAIN NEOPLASMS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; NEOVASCULARIZATION, PATHOLOGIC;

EID: 0041870830     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/942     Document Type: Review

References (128)

1. Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82, 4-6 (1990)
2. WK Cavenee, FB Furnari, M Nagane, H-JS Huang, EW Newcombe, DD Bigner, M Weller, ME Berens, KH Plate, MA Israel, MD Noble & P Kleihues: Diffusely infiltrating astrocytomas. In: Pathology and genetics of tumours of the nervous system. 2nd ed Eds: Kleihues P, Cavenee WK, International Agency for Research, Lyon, France, 10-21 (2000)
3. Burger PC & BW Scheithauer: Tumors of the central nervous system. Atlas of tumor pathology, 3rd Series, fascicle 10. Armed Forces Institute of Pathology, Washington, DC, 25-68 (1994)
4. Kleihues P, RL Davis, H Ohgaki, PC Burger, MM Westphal & Cavenee WK: Diffuse astrocytoma. In: Pathology and genetics of tumours of the nervous system. 2nd ed. Eds: Kleihues P, Cavenee WK, International Agency for Research, Lyon, France, 22-26 (2000)
5. Kleihues P, RL Davis, SW Coons & PC Burger: Anaplastic astrocytoma. In: Pathology and genetics of tumours of the nervous system. 2nd ed. Eds: Kleihues P, Cavenee WK, International Agency for Research, Lyon, France, 27-28 (2000)
6. Kleihues P, PC Burger, VP Collins, EW Newcomb, H Ohgaki & WK Cavenee: Glioblastoma. In: Pathology and genetics of tumours of the nervous system, 2nd ed. Eds: Kleihues P and Cavenee WK, International Agency for Research on Cancer, Lyon, France, 29-39 (2000)
7. von Deimling A, K von Ammon, D Schoenfeld, OD Wiestler, BR Seizinger & DN Louis: Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol 3, 19-26 (1993)
8. Carmeliet P & RK Jain: Angiogenesis in cancer and other diseases. Nature 407, 249-257 (2000)
9. Yancopoulos GD, S Davis, NW Gale, JS Rudge, SJ Wiegand & J Holash: Vascular-specific growth factors and blood vessel formation. Nature 407, 242-248 (2000)
10. Kerbel RS: Tumor angiogenesis: past, present and the near future. Carcinogenesis 21, 505-515 (2000)
11. Hanahan D & J Folkman: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86, 353-364 (1996)
12. Dvorak HF: VPF/VEGF and the angiogenic response. Semin Perinatol 24, 75-78 (2000)
13. Senger DR, SJ Galli, AM Dvorak, CA Perruzzi, VS Harvey & HF Dvorak: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219, 983-985 (1983)
14. Sundberg C, JA Nagy, LF Brown, D Feng, IA Eckelhoefer, AM Manseau & HF Dvorak: Glomeruloid microvascular proliferation follows adenoviral VPF/VEGF164 gene delivery. Am J Pathol 158, 1145-1160 (2001)
15. Brat DJ & EG Van Meir: Glomeruloid microvascular proliferation orchestrated by VPF/VEGF: a new world of angiogenesis research. Am J Pathol 158, 789-796 (2001)
16. Wesseling P, RO Schlingemann, FJ Rietveld, M Link, PC Burger & DJ Ruiter: Early and extensive contribution of pericytes/vascular smooth muscle cells to microvascular proliferation in glioblastoma multiforme: an immuno-light and immuno-electron microscopic study. J Neuropathol Exp Neurol 54, 304-310 (1995)
17. Ferrara N & T Davis-Smyth: The biology of vascular endothelial growth factor. Endocr Rev 18, 4-25 (1997)
18. Fukumura D, R Xavier, T Sugiura, Y Chen, EC Park, N Lu, M Selig, G Nielsen, T Taksir, RK Jain & B Seed: Tumor induction of VEGF promoter activity in stromal cells. Cell 94, 715-725 (1998)
19. Pettersson A, JA Nagy, LF Brown, C Sundberg, E Morgan, S Jungles, R Carter, JE Krieger, EJ Manseau, VS Harvey, IA Eckelhoefer, D Feng, AM Dvorak, RC Mulligan & HF Dvorak: Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Lab Invest 80, 99-115 (2000)
20. Eberhard A, S Kahlert, V Goede, B Hemmerlein, KH Plate & HG Augustin: Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res 60, 1388-1393 (2000)
21. Van Meir EG: Cytokines and tumors of the central nervous system. Glia 15, 264-288 (1995)
22. Desbaillets I, AC Diserens, N de Tribolet, MF Hamou & EG Van Meir: Regulation of interleukin-8 expression by reduced oxygen pressure in human glioblastoma. Oncogene 18, 1447-1456 (1999)
23. Desbaillets I, AC Diserens, N de Tribolet, MF Hamou & EG Van Meir: Upregulation of interleukin 8 by oxygen-deprived cells in glioblastoma suggests a role in leukocyte activation, chemotaxis, and angiogenesis. J Exp Med 186, 1201-1212 (1997)
24. Chan PT & RO Weller: Factors influencing tumor cell and vascular proliferation in glioblastoma. Neuropathol Appl Neurobiol 28, 155-156 (2002)
25. Plate KH: Mechanisms of angiogenesis in the brain. J Neuropathol Exp Neurol 58, 313-320 (1999)
26. Takano S, Y Yoshii, S Kondo, H Suzuki, T Maruno, S Shirai & T Nose: Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. Cancer Res 56, 2185-2190 (1996)
27. Veikkola T, M Karkkainen, L Claesson-Welsh & K Alitalo: Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res 60, 203-212 (2000)
28. Guo P, L Xu, S Pan, RA Brekken, ST Yang, GB Whitaker, M Nagane, PE Thorpe, JS Rosenbaum, HJ Su Huang, WK Cavenee & SY Cheng: Vascular endothelial growth factor isoforms display distinct activities in promoting tumor angiogenesis at different anatomic sites. Cancer Res 61, 8569-8577 (2001)
29. Robinson CJ & SE Stringer: The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 114, 853-865 (2001)
30. Plate KH, G Breier, HA Weich & W Risau: Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359, 845-848 (1992)
31. Shweiki D, A Itin, D Soffer & E Keshet: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359, 843-845 (1999)
32. Semenza GL: Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol Med 7, 345-350 (2001)
33. Zagzag D, H Zhong, JM Scalzitti, E Laughner, JW Simons & GL Semenza: Expression of hypoxia-inducible factor 1alpha in brain tumors: association with angiogenesis, invasion, and progression. Cancer 88, 2606-2618 (2000)
34. Kung AL, S Wang, JM Klco, WG Kaelin & DM Livingston: Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat Med 6, 1335-1340 (2000)
35. Damert A, M Machein, G Breier, MQ Fujita, D Hanahan, W Risau & KH Plate: Up-regulation of vascular endothelial growth factor expression in a rat glioma is conferred by two distinct hypoxia-driven mechanisms. Cancer Res 57, 3860-3864 (1997)
36. Maxwell PH, CW Pugh & PJ Ratcliffe: Activation of the HIF pathway in cancer. Curr Opin Genet Dev 11, 293-299 (2001)
37. Lal A, H Peters, B St Croix, ZA Haroon, MW Dewhirst, RL Strausberg, JH Kaanders, AJ van der Kogel & GJ Riggins: Transcriptional response to hypoxia in human tumors. J Natl Cancer Inst 93, 1337-1343 (2001)
38. Mazure NM, C Chauvet, B Bois-Joyeux, MA Bernard, H Nacer-Cherif & JL Danan: Repression of alpha- fetoprotein gene expression under hypoxic conditions in human hepatoma cells: characterization of a negative hypoxia response element that mediates opposite effects of hypoxia inducible factor-1 and c-Myc. Cancer Res 62, 1158-1165 (2002)
39. Wang GL, BH Jiang, EA Rue & GL Semenza: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92, 5510-5514 (1995)
40. Semenza GL: HIF-1 and human disease: one highly involved factor. Genes Dev 14, 1983-1991 (2000)
41. Kotch LE, NV Iyer, E Laughner & GL Semenza: Defective vascularization of HIF-1 alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol 209, 254-267 (1999)
42. Compernolle V, K Brusselmans, T Acker, P Hoet, M Tjwa, H Beck, S Plaisance, Y Dor, E Keshet, F Lupu, B Nemery, M Dewerchin, P Van Veldhoven, K Plate, L Moons, D Collen & P Carmeliet: Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med 8, 702-710 (2002)
43. Suzuki H, A Tomida & T Tsuruo: Dephosphorylated hypoxia-inducible factor 1alpha as a mediator of p53-dependent apoptosis during hypoxia. Oncogene 20, 5779-5788 (2001)
44. Jiang BH, E Rue, GL Wang, R Roe & GL Semenza: Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem 271, 17771-17778 (1996)
45. Pugh CW, JF O'Rourke, M Nagao, JM Gleadle & PJ Ratcliffe: Activation of hypoxia-inducible factor-1; definition of regulatory domains within the alpha subunit. J Biol Chem 272, 11205-11214 (1997)
46. Kallio PJ, K Okamoto, S O'Brien, P Carrero, Y Makino, H Tanaka & L Poellinger: Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia- inducible factor-1alpha. EMBO J 17, 6573-6586 (1998)
47. Wiener CM, G Booth & GL Semenza: In vivo expression of mRNAs encoding hypoxia-inducible factor 1. Biochem Biophys Res Commun 225, 485-488 (1996)
48. Kallio PJ, WJ Wilson, S O'Brien, Y Makino & L Poellinger: Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. J Biol Chem 274, 6519-6525 (1999)
49. Huang LE, J Gu, M Schau & HF Bunn: Regulation of hypoxia-inducible factor 1alpha is mediated by an O2- dependent degradation domain via the ubiquitin- proteasome pathway. Proc Natl Acad Sci USA 95, 7987-7992 (1998)
50. Maxwell PH, MS Wiesener, GW Chang, SC Clifford, EC Vaux, ME Cockman, CC Wykoff, CW Pugh, ER Maher & PJ Ratcliffe: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271-275 (1999)
51. Stebbins CE, WG Kaelin Jr & NP Pavletich: Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. Science 284, 455-461 (1999)
52. Ivan M, K Kondo, H Yang, W Kirn, J Valiando, M Ohh, A Salic, JM Asara, WS Lane & WG Kaelin Jr: HIF-1alpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292, 464-468 (2001)
53. Jaakkola P, DR Mole, YM Tian, MI Wilson, J Gielbert, SJ Gaskell, Av Kriegsheim, HF Hebestreit, M Mukherji, CJ Schofield, PH Maxwell, CW Pugh &PJ Ratcliffe: Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292, 468-472 (2001)
54. Epstein AC, JM Gleadle, LA McNeill, KS Hewitson, J O'Rourke, DR Mole, M Mukherji, E Metzen, MI Wilson, A Dhanda, YM Tian, N Masson, DL Hamilton, P Jaakkola, R Barstead, J Hodgkin, PH Maxwell, CW Pugh, CJ Schofield & PJ Ratcliffe. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107, 43-54 (2001)
55. Makino Y, R Cao, K Svensson, G Bertilsson, M Asman, H Tanaka, Y Cao, A Berkenstam & L Poellinger: Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 414, 550-554 (2001)
56. Lando D, DJ Peet, DA Whelan, JJ Gorman & ML Whitelaw: Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295, 858-861 (2002)
57. Hewitson KS, LA McNeill, MV Riordan, YM Tian, AN Bullock, RW Welford, JM Elkins, NJ Oldham, S Bhattacharya, JM Gleadle, PJ Ratcliffe, CW Pugh & CJ Schofield: Hypoxia inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem 277, 26351-26355 (2002)
58. Lando D, DJ Peet, JJ Gorman, DA Whelan, ML Whitelaw & Bruick. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 16, 1466-71 (2002)
59. Bhattacharya S, CL Michels, MK Leung, ZP Arany, AL Kung & DM Livingston: Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1. Genes Dev 13, 64-75 (1999)
60. Yin Z, J Haynie, X Yang, B Han, S Kiatchoosakun, J Restivo, S Yuan, NR Prabhakar, K Herrup, RA Conlon, BD Hoit, M Watanabe & YC Yang: The essential role of Cited2, a negative regulator for HIF-1alpha, in heart development and neurulation. Proc Natl Acad Sci U S A 99, 10488-10493 (2002)
61. Maxwell PH, GU Dachs, JM Gleadle, LG Nicholls, AL Harris, IJ Stratford, O Hankinson, CW Pugh & PJ Ratcliffe: Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 94, 8104-8109 (1997)
62. Mazure NM, EY Chen, P Yeh, KR Laderoute & AJ Giaccia: Oncogenic transformation and hypoxia synergistically act to modulate vascular endothelial growth factor expression. Cancer Res 56, 3436-3440 (1996)
63. Arbiser JL, MA Moses, CA Fernandez, N Ghiso, Y Cao, N Klauber, D Frank, M Brownlee, E Flynn, S Parangi, HR Byers & J Folkman: Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci U S A 94, 861-866 (1997)
64. Mazure NM, EY Chen, KR Laderoute & AJ Giaccia: Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood 90, 3322-3331 (1997)
65. Jiang BH, F Agani, A Passaniti & GL Semenza: V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Cancer Res 57, 5328-35 (1997)
66. Mukhopadhyay D, L Tsiokas, XM Zhou, D Foster, JS Brugge & VP Sukhatme: Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 375, 577-581 (1995)
67. Gleadle JM & PJ Ratcliffe: Induction of hypoxia-inducible factor-1, erythropoietin, vascular endothelial growth factor, and glucose transporter-1 by hypoxia: evidence against a regulatory role for Src kinase. Blood 89, 503-9 (1997)
68. Jiang BH, JZ Zheng, M Aoki & PK Vogt: Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci U S A 97, 1749-5173 (2000)
69. Zhong H, K Chiles, D Feldser, E Laughner, C Hanrahan, MM Georgescu, JW Simons & GL Semenza: Modulation of hypoxia-inducible factor 1 alpha expression by the epidermal growth factor/phosphatidylinositol 3- kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 60, 1541-1545 (2000)
70. Jiang BH, G Jiang, JZ Zheng, Z Lu, T Hunter & PK Vogt: Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ 12, 363-369 (2001)
71. Laughner E, P Taghavi, K Chiles, PC Mahon & GL Semenza: HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol 21, 3995-4004 (2001)
72. Treins C, S Giorgetti-Peraldi, J Murdaca, GL Semenza & E Van Obberghen: Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. J Biol Chem 277, 27975-27981 (2002)
73. Fulci G, N Ishii & EG Van Meir: p53 and brain tumors: from gene mutations to gene therapy. Brain Pathol 8, 599-613 (1998)
74. Van Meir EG, T Kikuchi, M Tada, H Li, AC Diserens, BE Wojcik, HJ Huang, T Friedmann & N de Tribolet, Cavenee WK: Analysis of the p53 gene and its expression in human glioblastoma cells. Cancer Res 54, 649-652 (1994)
75. Albertoni M, DM Daub, KC Arden, CS Viars, C Powell & EG Van Meir: Genetic instability leads to loss of both p53 alleles in a human glioblastoma. Oncogene 16, 321-326 (1998)
76. Reifenberger G, L Liu, K Ichimura, EE Schmidt & VP Collins: Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res 53, 2736-2739 (1993)
77. Fulci G, M Labuhn, D Maier, Y Lachat, O Hausmann, ME Hegi, RC Janzer, A Merlo & EG Van Meir: p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive events in human glioblastoma. Oncogene 19, 3816-3822 (2000)
78. Mukhopadhyay D, L Tsiokas & VP Sukhatme: Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res 55, 6161-6165 (1995)
79. Bouvet M, LM Ellis, M Nishizaki, T Fujiwara, W Liu, CD Bucana, B Fang, JJ Lee & JA Roth: Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human colon cancer. Cancer Res 58, 2288-2292 (1998)
80. Ravi R, B Mookerjee, ZM Bhujwalla, CH Sutter, D Artemov, Q Zeng, LE Dillehay, A Madan, GL Semenza & A Bedi: Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14, 34-44 (2000)
81. Blagosklonny MV, WG An, LY Romanova, J Trepel, T Fojo & L Neckers: p53 inhibits hypoxia-inducible factor-stimulated transcription. J Biol Chem 273, 11995-1198 (1998)
82. An WG, M Kanekal, MC Simon, E Maltepe, MV Blagosklonny & LM Neckers: Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature 392, 405-408 (1998)
83. Wenger RH, G Camenisch, I Desbaillets, D Chilov & M Gassmann: Up-regulation of hypoxia-inducible factor-1 alpha is not sufficient for hypoxic/anoxic p53 induction. Cancer Res 58, 5678-5680 (1998)
84. Hammond EM, NC Denko, MJ Dorie, RT Abraham & AJ Giaccia: Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol 22, 1834-1843 (2002)
85. Koumenis C, R Alarcon, E Hammond, P Sutphin, W Hoffman, M Murphy, J Derr, Y Taya, SW Lowe, M Kastan & A Giaccia: Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol 21, 1297-1310 (2001)
86. Weber JD, LJ Taylor, MF Roussel, CJ Sherr & Bar-Sagi: Nucleolar Arf sequesters Mdm2 and activates p53. Nat Cell Biol 1, 20-26 (1999)
87. Fatyol K & AA Szalay: The p14ARF tumor suppressor protein facilitates nucleolar sequestration of hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibits HIF-1-mediated transcription. J Biol Chem 276, 28421-28429 (2001)
88. McKeller RN, JL Fowler, JJ Cunningham, N Warner, RJ Smeyne, F Zindy & SX Skapek: The Arf tumor suppressor gene promotes hyaloid vascular regression during mouse eye development. Proc Natl Acad Sci USA 99, 3848-3853 (2002)
89. Ueba T, T Nosaka, JA Takahashi, F Shibata, RZ Florkiewicz, B Vogelstein, Y Oda, H Kikuchi & M Hatanaka: Transcriptional regulation of basic fibroblast growth factor gene by p53 in human glioblastoma and hepatocellular carcinoma cells. Proc Natl Acad Sci U S A 91, 9009-9013 (1994)
90. Takahashi JA, H Mori, M Fukumoto, K Igarashi, M Jaye, Y Oda, H Kikuchi & M Hatanaka: Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues. Proc Natl Acad Sci U S A 87, 5710-5714 (1990)
91. de Fraipont F, AC Nicholson, JJ Feige & EG Van Meir: Thrombospondins and tumor angiogenesis. Trends Mol Med 7, 401-407 (2001)
92. Dameron KM, OV Volpert, MA Tainsky & N Bouck: Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265, 1582-1584 (1994)
93. Tenan M, G Fulci, M Albertoni, AC Diserens, MF Hamou, M El Atifi-Borel, JJ Feige, MS Pepper & EG Van Meir: Thrombospondin-1 is downregulated by anoxia and suppresses tumorigenicity of human glioblastoma cells. J Exp Med 191, 1789-98 (2000)
94. Van Meir EG, PJ Polverini, VR Chazin, HJ Su Huang, N de Tribolet & WK Cavenee: Release of an inhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cells. Nat Genet 8, 171-176 (1994)
95. Nishimori H, T Shiratsuchi, T Urano, Y Kimura, K Kiyono, K Tatsumi, S Yoshida, M Ono, M Kuwano, Y Nakamura & T Tokino: A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene 15, 2145-2150 (1997)
96. Kaur B, DJ Brat, CC Calkins & EG Van Meir: Brain angiogenesis inhibitor-1 (BAI1) is differentially expressed in normal brain and glioblastoma independently of p53 expression. Am J Pathol (in press)
97. Li J, C Yen, D Liaw, K Podsypanina, S Bose, SI Wang, J Pue, C Miliaresis, L Rodgers, R McCombie, SH Bigner, BC Giovanella, M Ittmann, B Tycko, H Hibshoosh, MH Wigler & R Parsons: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943-1947 (1997)
98. Steck PA, MA Pershouse, SA Jasser, WK Yung, H Lin, AH Ligon, LA Langford, ML Baumgard, T Hattier, T Davis, C Frye, R Hu, B Swedlund, DH Teng & SV Tavtigian: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15, 356-362 (1997)
99. Cantley LC & BG Neel: New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 96, 4240-4245 (1999)
100. Zundel W, C Schindler, D Haas-Kogan, A Koong, F Kaper, E Chen, AR Gottschalk, HE Ryan, RS Johnson, AB Jefferson, D Stokoe & AJ Giaccia: Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev 14, 391-396 (2000)
101. Mahon PC, K Hirota & GL Semenza: FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev 15, 2675-86 (2001)
102. Hsu SC, OV Volpert, PA Steck, T Mikkelsen, PJ Polverini, S Rao, P Chou & NP Bouck: Inhibition of angiogenesis in human glioblastomas by chromosome 10 induction of thrombospondin-1. Cancer Res 56, 5684-91 (1996)
103. Wen S, J Stolarov, MP Myers, JD Su, MH Wigler, NK Tonks & DL Durden: PTEN controls tumor-induced angiogenesis. Proc Natl Acad Sci U S A 98, 4622-4627 (2001)
104. Schlessinger J: Cell signaling by receptor tyrosine kinases. Cell 103, 211-225 (2000)
105. Ekstrand AJ, CD James, WK Cavenee, B Seliger, RF Pettersson & VP Collins: Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 51, 2164-2172 (1991)
106. Frederick L, XY Wang, G Eley & CD James: Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 60, 1383-1387 (2000)
107. Nishi H, KH Nishi & AC Johnson: Early Growth Response-1 gene mediates up-regulation of epidermal growth factor receptor expression during hypoxia. Cancer Res 62, 827-834 (2002)
108. Clarke K, K Smith, WJ Gullick & AL Harris: Mutant epidermal growth factor receptor enhances induction of vascular endothelial growth factor by hypoxia and insulin-like growth factor-1 via a PB kinase dependent pathway. Br J Cancer 84, 1322-1329 (2001)
109. Maity A, N Pore, J Lee, D Solomon & DM O'Rourke. Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3′-kinase and distinct from that induced by hypoxia. Cancer Res 60, 5879-5886 (2000)
110. Westermark B, CH Heldin & M Nister: Platelet-derived growth factor in human gliomas. Glia 15, 257-263 (1995)
111. Hermanson M, K Funa, M Hartman, L Claesson-Welsh, CH Heldin, B Westermark & M Nistér: Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res 52, 3213-3219 (1992)
112. Fleming TP, A Saxena, WC Clark, JT Robertson, EH Oldfield, SA Aaronson & IU Ali: Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res 52, 4550-4553 (1992)
113. Wang D, HJS Huang, A Kazlauskas & WK Cavenee: Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase. Cancer Res 59:1464-1472 (1999)
114. Franke TF, SI Yang, TO Chan, K Datta, A Kazlauskas, DK Morrison, DR Kaplan & PN Tsichlis: The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 81, 727-36 (1995)
115. Chen EY, NM Mazure, JA Cooper & AJ Giaccia: Hypoxia activates a platelet-derived growth factor receptor/phosphatidylinositol 3-kinase/Akt pathway that results in glycogen synthase kinase-3 inactivation. Cancer Res 61, 2429-2433 (2001)
116. Schmidt EE, K Ichimura, G Reifenberger & VP Collins: CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas. Cancer Res 54, 6321-6324 (1994)
117. Costello JF, C Plass, W Arap, VM Chapman, WA Held, MS Berger, HJS Huang, & WK Cavenee: Cyclin-dependent kinase 6 (CDK6) amplification in human gliomas identified using two-dimensional separation of genomic DNA. Cancer Res 57, 1250-1254 (1997)
118. Harada H, K Nakagawa, S Iwata, M Saito, Y Kumon, S Sakaki, K Sato & K Hamada: Restoration of wild-type p16 down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human gliomas. Cancer Res 59, 3783-3789 (1999)
119. Ivan M & WG Kaelin Jr: The von Hippel-Lindau tumor suppressor protein. Curr Opin Genet Dev 11, 27-34 (2001)
120. Krieg M, R Haas, H Brauch, T Acker, I Flamme & KH Plate: Up-regulation of hypoxia-inducible factors HIF-1 alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene 19, 5435-5443 (2000)
121. Wizigmann-Voos S, G Breier, W Risau & KH Plate: Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas. Cancer Res 55, 1358-1364 (1995)
122. Flamme I, M Krieg & KH Plate: Up-regulation of vascular endothelial growth factor in stromal cells of hemangioblastomas is correlated with up-regulation of the transcription factor HRF/HIF-2alpha. Am J Pathol 153, 25-29 (1998)
123. Rapisarda A, B Uranchimeg, DA Scudiero, M Selby, EA Sausville, RH Shoemaker & G Melillo: Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway. Cancer Res 62, 4316-4324 (2002)
124. Mabjeesh NJ, DE Post, MT Willard, B Kaur, EG Van Meir, JW Simons & H Zhong: Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells. Cancer Res 62, 2478-2482 (2002)
125. Post DE & EG Van Meir: Generation of bidirectional hypoxia/HIF-responsive expression vectors to target gene expression to hypoxic cells. Gene Ther 8, 1801-1807 (2001)
126. Dang LH, C Bettegowda, DL Huso, KW Kinzler & B Vogelstein: Combination bacteriolytic therapy for the treatment of experimental tumors. Proc Natl Acad Sci U S A 98, 15155-15160 (2001)
127. Gabrilovich D, T Ishida, T Oyama, S Ran, V Kravtsov, S Nadaf & DP Carbone: Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92, 4150-4166 (1998)
128. Oosthuyse B, L Moons, E Storkebaum, H Beck, D Nuyens, K Brusselmans, J Van Dorpe, P Hellings, M Gorselink, S Heymans, G Theilmeier, M Dewerchin, V Laudenbach, P Vermylen, H Raat, T Acker, V Vleminckx, L Van Den Bosch, N Cashman, H Fujisawa, MR Drost, R Sciot, F Bruyninckx, DJ Hicklin, C Ince, P Gressens, F Lupu, KH Plate, W Robberecht, JM Herbert, D Collen & P Carmeliet: Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 28, 131-138 (2001)