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Transformation of Normal Astrocytes Into a Tumor Phenotype

  • Chapter
The Cell Cycle in the Central Nervous System

Part of the book series: Contemporary Neuroscience ((CNEURO))

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Abstract

Genetic alterations leading to changes in cell cycle regulation and growth factor signaling transform astrocytes into a tumor phenotype. This chapter describes four grades of astrocytic tumors, discusses how genetic alterations lead to astrocyte transformation, and stresses how growth factor and cell cycle signaling networks contribute to this transformation. Finally we discuss cell lines and animal models pertinent to the study of astrocytic tumors.

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References

  1. Arenander A, de Vellis J. Early response gene induction in astrocytes as a mechanism for encoding and integrating neuronal signals. Prog Brain Res 1992;94:177–188.

    Article  PubMed  CAS  Google Scholar 

  2. Bentivoglio M, Mazzarello P. The history of radial glia. Brain Res Bull 1999;49:305–315.

    Article  PubMed  CAS  Google Scholar 

  3. Hatten ME, Mason CA. Mechanisms of glial-guided neuronal migration in vitro and in vivo. Experientia 1990;46:907–916.

    Article  PubMed  CAS  Google Scholar 

  4. Komuro H, Rakic P. Distinct modes of neuronal migration in different domains of developing cerebellar cortex. J Neurosci 1998;18:1478–1490.

    PubMed  CAS  Google Scholar 

  5. Mason CA, Sretavan DW. Glia, neurons, and axon pathfinding during optic chiasm development. Curr Opin Neurobiol 1997;7:647–653.

    Article  PubMed  CAS  Google Scholar 

  6. Powell EM, Meiners S, DiProspero NA, Geller HM. Mechanisms of astrocyte-directed neurite guidance. Cell Tissue Res 1997;290:385–393.

    Article  PubMed  CAS  Google Scholar 

  7. van den Pol AN, Spencer DD. Differential neurite growth on astrocyte substrates: interspecies facilitation in green fluorescent protein-transfected rat and human neurons. Neuroscience 2000;95:603–616.

    PubMed  Google Scholar 

  8. Araque A, Sanzgiri RP, Parpura V, Haydon PG. Astrocyte-induced modulation of synaptic transmission. Can J Physiol Pharmacol 1999;77:699–706.

    Article  PubMed  CAS  Google Scholar 

  9. Bacci A, Verderio C, Pravettoni E, Matteoli M. The role of glial cells in synaptic function. Philos Trans R Soc Lond B Biol Sci 1999;354:403–409.

    Article  PubMed  CAS  Google Scholar 

  10. Pfrieger FW, Barres BA. New views on synapse-glia interactions. Curr Opin Neurobiol 1996:6:615–621.

    Article  PubMed  CAS  Google Scholar 

  11. Vesce S, Bezzi P, Volterra A. The active role of astrocytes in synaptic transmission. Cell Mol Life Sci 1999;56:991–1000.

    Article  PubMed  CAS  Google Scholar 

  12. Aschner M. Immune and inflammatory responses in the CNS: modulation by astrocytes. Toxicol Lett 1998:102–103:283–287.

    Article  PubMed  Google Scholar 

  13. Montgomery DL. Astrocytes: form, functions, and roles in disease. Vet Pathol 1994;31:145–167.

    Article  PubMed  CAS  Google Scholar 

  14. Walter AW, Hancock ML, Pui CH, et al. Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children’s Research Hospital. J Clin Oncol 1998;16:3761–3767.

    PubMed  CAS  Google Scholar 

  15. Neglia JP, Meadows AT, Robison LL, et al. Second neoplasms after acute lymphoblastic leukemia in childhood. N Engl J Med 1991;325:1330–1336.

    Article  PubMed  CAS  Google Scholar 

  16. Brada M, Ford D, Ashley S, et al. Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. BMJ 1992;304:1343–1346.

    Article  PubMed  CAS  Google Scholar 

  17. Louis DN, von Deimling A. Hereditary tumor syndromes of the nervous system: overview and rare syndromes. Brain Pathol 1995;5:145–151.

    Article  PubMed  CAS  Google Scholar 

  18. Simpson JR, Horton J, Scott C, et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 1993;26:239–244.

    PubMed  CAS  Google Scholar 

  19. McCormack BM, Miller DC, Budzilovich GN, Voorhees GJ, Ransohoff J. Treatment and survival of low-grade astrocytoma in adults—1977–1988. Neurosurgery 1992;31:636–642; discussion 642.

    Article  PubMed  CAS  Google Scholar 

  20. Ding H, Shannon P, Lau N, et al. Oligodendrogliomas result from the expression of an activated mutant epidermal growth factor receptor in a RAS transgenic mouse astrocytoma model. Cancer Res 2003;63:1106–1113.

    PubMed  CAS  Google Scholar 

  21. Mueller W, Hartmann C, Hoffmann A, et al. Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets. Am J Pathol 2002;161:313–319.

    PubMed  CAS  Google Scholar 

  22. Hartwell L. Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells. Cell 1992;71:543–546.

    Article  PubMed  CAS  Google Scholar 

  23. Lane DP. Cancer. p53, guardian of the genome. Nature 1992;358:15,16.

    Article  PubMed  CAS  Google Scholar 

  24. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990;250:1233–1238.

    Article  PubMed  CAS  Google Scholar 

  25. Hermanson M, Funa K, Hartman M, et al. 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 1992;52:3213–3219.

    PubMed  CAS  Google Scholar 

  26. Nishizaki T, Ozaki S, Harada K, et al. Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization. Genes Chromosomes Cancer 1998;21:340–346.

    Article  PubMed  CAS  Google Scholar 

  27. Schrock E, Blume C, Meffert MC, du Manoir S, Bersch W, Kiessling M. Recurrent gain of chromosome arm 7q in low-grade astrocytic tumors studied by comparative genomic hybridization. Genes Chromosomes Cancer 1996;15:199–205.

    Article  PubMed  CAS  Google Scholar 

  28. Zulch K. Brain Tumors. Their Biology and Pathology. 3rd ed. Berlin, Heidelberg: Springer-Verlag; 1986.

    Google Scholar 

  29. Ohgaki H, Watanabe K, Peraud A, et al. A case history of glioma progression. Acta Neuropathol (Berl) 1999;97:525–532.

    Article  CAS  Google Scholar 

  30. Gonzalez-Gomez P, Bello MJ, Arjona D, et al. Promoter hypermethylation of multiple genes in astrocytic gliomas. Int J Oncol 2003;22:601–608.

    PubMed  CAS  Google Scholar 

  31. Nakamura M, Watanabe T, Yonekawa Y, Kleihues P, Ohgaki H. Promoter methylation of the DNA repair gene MGMT in astrocytomas is frequently associated with G:C ≥ A:T mutations of the TP53 tumor suppressor gene. Carcinogenesis 2001;22:1715–1719.

    Article  PubMed  CAS  Google Scholar 

  32. Nakamura M, Watanabe T, Klangby U, Asker C, Wiman K, Yonekawa Y. pl4ARF deletion and methylation in genetic pathways to glioblastomas. Brain Pathol 2001;11:159–168.

    Article  PubMed  CAS  Google Scholar 

  33. Matsumoto K, Suzuki SO, Fukui M, Iwaki T. Accumulation of MDM2 in pleomorphic xanthoastro-cytomas. Pathol Int 2004;54:387–391.

    Article  PubMed  CAS  Google Scholar 

  34. Paulus W, Lisle DK, Tonn JC, et al. Molecular genetic alterations in pleomorphic xanthoastrocy-toma. Acta Neuropathol (Berl) 1996;91:293–297.

    Article  CAS  Google Scholar 

  35. Sharma M, Ralte A, Arora R, Santosh V, Shankar SK, Sarkar C. Subependymal giant cell astrocytoma: a clinicopathological study of 23 cases with special emphasis on proliferative markers and expression of p53 and retinoblastoma gene proteins. Pathology 2004;36:139–144.

    Article  PubMed  CAS  Google Scholar 

  36. Kim SK, Wang KC, Cho BK, et al. Biological behavior and tumorigenesis of subependymal giant cell astrocytomas. J Neurooncol 2001;52:217–225.

    Article  PubMed  CAS  Google Scholar 

  37. Plank TL, Yeung RS, Henske EP. Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. Cancer Res 1998;58:4766–4770.

    PubMed  CAS  Google Scholar 

  38. Inoki K, Li Y, Xu T, Guan KL. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 2003;17:1829–1834.

    Article  PubMed  CAS  Google Scholar 

  39. Ekstrand AJ, James CD, Cavenee WK, Seliger B, Pettersson RF, Collins VP. Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 1991;51:2164–2172.

    PubMed  CAS  Google Scholar 

  40. Frederick L, Wang XY, Eley G, James CD. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 2000;60:1383–1387.

    PubMed  CAS  Google Scholar 

  41. Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci USA 1992;89:2965–2969.

    Article  PubMed  CAS  Google Scholar 

  42. Ekstrand AJ, Sugawa N, James CD, Collins VP. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N-and/or C-terminal tails. Proc Natl Acad Sci USA 1992;89:4309–4313.

    Article  PubMed  CAS  Google Scholar 

  43. Sugawa N, Ekstrand AJ, James CD, Collins VP. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci USA 1990;87:8602–8606.

    Article  PubMed  CAS  Google Scholar 

  44. Holland EC, Hively WP, DePinho RA, Varmus HE. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev 1998;12:3675–3685.

    Article  PubMed  CAS  Google Scholar 

  45. Uhrbom L, Hesselager G, Nister M, Westermark B. Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus. Cancer Res 1998;58:5275–5279.

    PubMed  CAS  Google Scholar 

  46. Guha A, Feldkamp MM, Lau N, Boss G, Pawson A. Proliferation of human malignant astrocytomas is dependent on Ras activation. Oncogene 1997;15:2755–2765.

    Article  PubMed  CAS  Google Scholar 

  47. Guha A. Ras activation in astrocytomas and neurofibromas. Can J Neurol Sci 1998;25:267–281.

    PubMed  CAS  Google Scholar 

  48. Haas-Kogan D, Shalev N, Wong M, Mills G, Yount G, Stokoe D. Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. Curr Biol 1998;8:1195–1198.

    Article  PubMed  CAS  Google Scholar 

  49. Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet 2000;25:55–57.

    Article  PubMed  CAS  Google Scholar 

  50. Bos JL. ras oncogenes in human cancer: a review. Cancer Res 1989;49:4682–4689.

    PubMed  CAS  Google Scholar 

  51. Weissenberger J, Steinbach JP, Malin G, Spada S, Rulicke T, Aguzzi A. Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene 1997;14:2005–2013.

    Article  PubMed  CAS  Google Scholar 

  52. Ding H, Roncari L, Shannon P, et al. Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas. Cancer Res 2001;61:3826–3836.

    PubMed  CAS  Google Scholar 

  53. Tohma Y, Gratas C, Biernat W, et al. PTEN (MMAC1) mutations are frequent in primary glioblastomas (de novo) but not in secondary glioblastomas. J Neuropathol Exp Neurol 1998;57:684–689.

    Article  PubMed  CAS  Google Scholar 

  54. Sonoda Y, Ozawa T, Hirose Y, et al. Formation of intracranial tumors by genetically modified human astrocytes defines four pathways critical in the development of human anaplastic astrocytoma. Cancer Res 2001;61:4956–4960.

    PubMed  CAS  Google Scholar 

  55. Choe G, Horvath S, Cloughesy TF, et al. Analysis of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res 2003;63:2742–2746.

    PubMed  CAS  Google Scholar 

  56. Rajasekhar VK, Viale A, Socci ND, Wiedmann M, Hu X, Holland EC. Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes. Mol Cell 2003;12:889–901.

    Article  PubMed  CAS  Google Scholar 

  57. Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 1988;334:661–665.

    Article  PubMed  CAS  Google Scholar 

  58. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 1984;308:693–698.

    Article  PubMed  CAS  Google Scholar 

  59. Gescher A. Towards selective pharmacological modulation of protein kinase C—opportunities for the development of novel antineoplastic agents. Br J Cancer 1992;66:10–19.

    PubMed  CAS  Google Scholar 

  60. Basu A. The potential of protein kinase C as a target for anticancer treatment. Pharmacol Ther 1993;59:257–280.

    Article  PubMed  CAS  Google Scholar 

  61. Blobe GC, Obeid LM, Hannun YA. Regulation of protein kinase C and role in cancer biology. Cancer Metastasis Rev 1994;13:411–431.

    Article  PubMed  CAS  Google Scholar 

  62. Choe Y, Jung H, Khang I, Kim K. Selective roles of protein kinase C isoforms on cell motility of GT1 immortalized hypothalamic neurones. J Neuroendocrinol 2003;15:508–515.

    Article  PubMed  CAS  Google Scholar 

  63. Couldwell WT, Uhm JH, Antel JP, Yong VW. Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro. Neurosurgery 1991;29:880–886; discussion 886–887.

    Article  PubMed  CAS  Google Scholar 

  64. Todo T, Shitara N, Nakamura H, Takakura K, Ikeda K Immunohistochemical demonstration of protein kinase C isozymes in human brain tumors. Neurosurgery 1991;29:399–403; discussion 403–404.

    Article  PubMed  CAS  Google Scholar 

  65. Benzil DL, Finkelstein SD, Epstein MH, Finch PW. Expression pattern of alpha-protein kinase C in human astrocytomas indicates a role in malignant progression. Cancer Res 1992;52:2951–2956.

    PubMed  CAS  Google Scholar 

  66. da Rocha AB, Mans DR, Lenz G, et al. Protein kinase C-mediated in vitro invasion of human glioma cells through extracellular-signal-regulated kinase and ornithine decarboxylase. Pathobiology 2000;68:113–123.

    Article  PubMed  Google Scholar 

  67. Mandil R, Ashkenazi E, Blass M, et al. Protein kinase Calpha and protein kinase Cdelta play opposite roles in the proliferation and apoptosis of glioma cells. Cancer Res 2001;61:4612–4619.

    PubMed  CAS  Google Scholar 

  68. Aeder SE, Martin PM, Soh JW, Hussaini IM. PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene 2004;23(56):9062–9069.

    Article  PubMed  CAS  Google Scholar 

  69. Hussaini IM, Carpenter JE, Redpath GT, Sando JJ, Shaffrey ME, Vandenberg SR. Protein kinase C-eta regulates resistance to UV-and gamma-irradiation-induced apoptosis in glioblastoma cells by preventing caspase-9 activation. Neurooncol 2002;4:9–21.

    CAS  Google Scholar 

  70. Hussaini IM, Karns LR, Vinton G, et al. Phorbol 12-myristate 13-acetate induces protein kinase ceta-specific proliferative response in astrocytic tumor cells. J Biol Chem 2000;275:22,348–22,354.

    Article  PubMed  CAS  Google Scholar 

  71. Tsai JC, Teng LJ, Chen CT, Hong TM, Goldman CK, Gillespie GY. Protein kinase C mediates induced secretion of vascular endothelial growth factor by human glioma cells. Biochem Biophys Res Commun 2003;309:952–960.

    Article  PubMed  CAS  Google Scholar 

  72. Park MJ, Park IC, Hur JH, et al. Protein kinase C activation by phorbol ester increases in vitro invasion through regulation of matrix metalloproteinases/tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells. Neurosci Lett 2000;290:201–204.

    Article  PubMed  CAS  Google Scholar 

  73. Park MJ, Park IC, Hur JH, et al. Modulation of phorbol ester-induced regulation of matrix metalloproteinases and tissue inhibitors of metalloproteinases by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase. J Neurosurg 2002;97:112–118.

    Article  PubMed  CAS  Google Scholar 

  74. Shih SC, Mullen A, Abrams K, Mukhopadhyay D, Claffey KP. Role of protein kinase C isoforms in phorbol ester-induced vascular endothelial growth factor expression in human glioblastoma cells. J Biol Chem 1999;274:15,407–15,414.

    Article  PubMed  CAS  Google Scholar 

  75. Plate KH, Breier G, Farrell CL, Risau W. Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab Invest 1992;67:529–534.

    PubMed  CAS  Google Scholar 

  76. Plate KH, Breier G, Risau W. Molecular mechanisms of developmental and tumor angiogenesis. Brain Pathol 1994;4:207–218.

    Article  PubMed  CAS  Google Scholar 

  77. Plate KH, Breier G, Weich HA, Mennel HD, Risau W. Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. Int J Cancer 1994;59:520–529.

    Article  PubMed  CAS  Google Scholar 

  78. Plate KH, Risau W. Angiogenesis in malignant gliomas. Glia 1995;15:339–347.

    Article  PubMed  CAS  Google Scholar 

  79. Hatva E, Kaipainen A, Mentula P, et al. Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors. Am J Pathol 1995;146:368–378.

    PubMed  CAS  Google Scholar 

  80. Chan AS, Leung SY, Wong MP, et al. Expression of vascular endothelial growth factor and its receptors in the anaplastic progression of astrocytoma, oligodendroglioma, and ependymoma. Am J Surg Pathol 1998;22:816–826.

    Article  PubMed  CAS  Google Scholar 

  81. Berkman RA, Merrill MJ, Reinhold WC, et al. Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. J Clin Invest 1993;91:153–159.

    Article  PubMed  CAS  Google Scholar 

  82. Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 1992;359:845–848.

    Article  PubMed  CAS  Google Scholar 

  83. Yoshiji H, Kuriyama S, Ways DK, et al. Protein kinase C lies on the signaling pathway for vascular endothelial growth factor-mediated tumor development and angiogenesis. Cancer Res 1999;59:4413–4418.

    PubMed  CAS  Google Scholar 

  84. Teicher BA, Menon K, Alvarez E, Galbreath E, Shih C, Faul M. Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human T98G glioblastoma multiforme xenografts. Clin Cancer Res 2001;7:634–640.

    PubMed  CAS  Google Scholar 

  85. Kleihues P, Ohgaki H. Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-Oncol 1999;1:44–51.

    Article  PubMed  CAS  Google Scholar 

  86. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993;366:704–707.

    Article  PubMed  CAS  Google Scholar 

  87. James CD, He J, Carlbom E, Nordenskjold M, Cavenee WK, Collins VP. Chromosome 9 deletion mapping reveals interferon alpha and interferon beta-1 gene deletions in human glial tumors. Cancer Res 1991;51:1684–1688.

    PubMed  CAS  Google Scholar 

  88. Olopade OI, Jenkins RB, Ransom DT, et al. Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas. Cancer Res 1992;52:2523–2529.

    PubMed  CAS  Google Scholar 

  89. Nishikawa R, Furnari FB, Lin H, et al. Loss of P16INK4 expression is frequent in high grade gliomas. Cancer Res 1995;55:1941–1945.

    PubMed  CAS  Google Scholar 

  90. Reifenberger G, Reifenberger J, Ichimura K, Meltzer PS, Collins VP. Amplification of multiple genes from chromosomal region 12ql3–14 in human malignant gliomas: preliminary mapping of the ampli-cons shows preferential involvement of CDK4, SAS, and MDM2. Cancer Res 1994;54:4299–4303.

    PubMed  CAS  Google Scholar 

  91. Guimaraes DP, Hainaut P. TP53: a key gene in human cancer. Biochimie 2002;84:83–93.

    Article  PubMed  CAS  Google Scholar 

  92. Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996;87:159–170.

    Article  PubMed  CAS  Google Scholar 

  93. Jacks T, Remington L, Williams BO, et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol 1994;4:1–7.

    Article  PubMed  CAS  Google Scholar 

  94. Donehower LA, Harvey M, Slagle BL, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992;356:215–221.

    Article  PubMed  CAS  Google Scholar 

  95. Sherr CJ, McCormick F. The RB and p53 pathways in cancer. Cancer Cell 2002;2:103–112.

    Article  PubMed  CAS  Google Scholar 

  96. Watanabe K, Sato K, Biernat W, et al. Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies. Clin Cancer Res 1997;3:523–530.

    PubMed  CAS  Google Scholar 

  97. Srivastava S, Zou ZQ, Pirollo K, Blattner W, Chang EH Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 1990;348:747–749.

    Article  PubMed  CAS  Google Scholar 

  98. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature 1997;387:296–299.

    Article  PubMed  CAS  Google Scholar 

  99. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature 1997;387:299–303.

    Article  PubMed  CAS  Google Scholar 

  100. Zauberman A, Flusberg D, Haupt Y, Barak Y, Oren M. A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res 1995;23:2584–2592.

    Article  PubMed  CAS  Google Scholar 

  101. Xiao ZX, Chen J, Levine AJ, et al. Interaction between the retinoblastoma protein and the oncoprotein MDM2. Nature 1995;375:694–8.

    Article  PubMed  CAS  Google Scholar 

  102. Mao L, Merlo A, Bedi G, et al. A novel pl6INK4A transcript. Cancer Res 1995;55:2995–2997.

    PubMed  CAS  Google Scholar 

  103. Quelle DE, Cheng M, Ashmun RA, Sherr CJ. Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by pl6INK4a but not by the alternative reading frame protein pl9ARF. Proc Natl Acad Sci USA 1997;94:669–673.

    Article  PubMed  CAS  Google Scholar 

  104. Stott FJ, Bates S, James MC, et al. The alternative product from the human CDKN2A locus, pl4(ARF), participates in a regulatory feedback loop with p53 and MDM2. EMBO J 1998;17:5001–5014.

    Article  PubMed  CAS  Google Scholar 

  105. Kamijo T, Zindy F, Roussel MF, et al. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product pl9ARF. Cell 1997;91:649–659.

    Article  PubMed  CAS  Google Scholar 

  106. Arap W, Knudsen E, Sewell DA, et al. Functional analysis of wild-type and malignant glioma derived CDKN2Abeta alleles: evidence for an RB-independent growth suppressive pathway. Oncogene 1997;15:2013–2020.

    Article  PubMed  CAS  Google Scholar 

  107. Tao W, Levine AJ. P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2. Proc Natl Acad Sci USA 1999;96:6937–6941.

    Article  PubMed  CAS  Google Scholar 

  108. Kamijo T, Bodner S, van de Kamp E, Randle DH, Sherr CJ. Tumor spectrum in ARF-deficient mice. Cancer Res 1999;59:2217–2222.

    PubMed  CAS  Google Scholar 

  109. Biernat W, Tohma Y, Yonekawa Y, Kleihues P, Ohgaki H. Alterations of cell cycle regulatory genes in primary (de novo) and secondary glioblastomas. Acta Neuropathol (Berl) 1997;94:303–309.

    Article  CAS  Google Scholar 

  110. Zhu Y, Parada LF. The molecular and genetic basis of neurological tumours. Nat Rev Cancer 2002;2:616–626.

    Article  PubMed  CAS  Google Scholar 

  111. Reilly KM, Loisel DA, Bronson RT, McLaughlin ME, Jacks T. Nfl;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat Genet 2000;26:109–113.

    Article  PubMed  CAS  Google Scholar 

  112. Shiseki M, Nagashima M, Pedeux RM, et al. p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res 2003;63:2373–2378.

    PubMed  CAS  Google Scholar 

  113. Garkavtsev I, Kozin SV, Chernova O, et al. The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature 2004;428:328–332.

    Article  PubMed  CAS  Google Scholar 

  114. Holland EC. Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet 2001;2:120–129.

    Article  PubMed  CAS  Google Scholar 

  115. Reilly KM, Jacks T. Genetically engineered mouse models of astrocytoma: GEMs in the rough? Semin Cancer Biol 2001;11:177–191.

    Article  PubMed  CAS  Google Scholar 

  116. Begemann M, Fuller GN, Holland EC. Genetic modeling of glioma formation in mice. Brain Pathol 2002;12:117–132.

    Article  PubMed  CAS  Google Scholar 

  117. Hesselager G, Holland EC. Using mice to decipher the molecular genetics of brain tumors. Neurosurgery 2003;53:685–694; discussion 695.

    Article  PubMed  Google Scholar 

  118. Gutmann DH, Baker SJ, Giovannini M, Garbow J, Weiss W. Mouse models of human cancer consortium symposium on nervous system tumors. Cancer Res 2003;63:3001–3004.

    PubMed  CAS  Google Scholar 

  119. Finkelstein SD, Black P, Nowak TP, Hand CM, Christensen S, Finch PW. Histological characteristics and expression of acidic and basic fibroblast growth factor genes in intracerebral xenogeneic transplants of human glioma cells. Neurosurgery 1994;34:136–143.

    Article  PubMed  CAS  Google Scholar 

  120. Joy AM, Beaudry CE, Tran NL, Ponce FA, Holz DR, Demuth T. Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis. J Cell Sci 2003;116:4409–4417.

    Article  PubMed  CAS  Google Scholar 

  121. Bernstein JJ, Goldberg WJ, Laws ER, Jr. Human malignant astrocytoma xenografts migrate in rat brain: a model for central nervous system cancer research. J Neurosci Res 1989;22:134–143.

    Article  PubMed  CAS  Google Scholar 

  122. Grobben B, De Deyn PP, Siegers H. Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion. Cell Tissue Res 2002;310:257–270.

    Article  PubMed  CAS  Google Scholar 

  123. Barth RF. Rat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas. J Neurooncol 1998;36:91–102.

    Article  PubMed  CAS  Google Scholar 

  124. Peterson DL, Sheridan PJ, Brown WE, Jr. Animal models for brain tumors: historical perspectives and future directions. J Neurosurg 1994;80:865–876.

    Article  PubMed  CAS  Google Scholar 

  125. Guillamo JS, Lisovoski F, Christov C, et al. Migration pathways of human glioblastoma cells xenografted into the immunosuppressed rat brain. J Neurooncol 2001;52:205–215.

    Article  PubMed  CAS  Google Scholar 

  126. Collins VP. Brain tumours: classification and genes. J Neurol Neurosurg Psychiatry 2004;75(Suppl 2):ii2–ii11.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Virginia, Charlottesville, VA

    Sean E. Aeder PhD & Isa M. Hussaini PhD

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  1. Sean E. Aeder PhD
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  2. Isa M. Hussaini PhD
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Editors and Affiliations

  1. The Cleveland Clinic Foundation, Cleveland, OH

    Damir Janigro PhD

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© 2006 Humana Press Inc., Totowa, NJ

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Aeder, S.E., Hussaini, I.M. (2006). Transformation of Normal Astrocytes Into a Tumor Phenotype. In: Janigro, D. (eds) The Cell Cycle in the Central Nervous System. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-59745-021-8_30

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