Myc proteins in brain tumor development and maintenance

Upsala Journal of Medical Sciences

Volumn 117, Issue 2, 2012, Pages 122-131

  Swartling, Fredrik J ^a  

^a UPPSALA UNIVERSITY   (Sweden)

Author keywords

Brain tumors; Molecular biology; Oncogenes; Pediatrics; Protein phosphorylation; Tumor biology

Indexed keywords

MYC PROTEIN;

ANIMAL; BRAIN; BRAIN TUMOR; GENETICS; GLIOBLASTOMA; HUMAN; MEDULLOBLASTOMA; METABOLISM; MOUSE; MUTATION; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; BRAIN; BRAIN NEOPLASMS; GLIOBLASTOMA; HUMANS; MEDULLOBLASTOMA; MICE; MUTATION; PROTO-ONCOGENE PROTEINS C-MYC; SIGNAL TRANSDUCTION;

EID: 84859911901     PISSN: 03009734     EISSN: None     Source Type: Journal    
DOI: 10.3109/03009734.2012.658975     Document Type: Review

References (144)

1. Eilers M, Eisenman RN. Myc's broad reach. Genes Dev. 2008;22:2755-66.
2. Stanton BR, Perkins AS, Tessarollo L, Sassoon DA, Parada LF. Loss of N-myc function results in embryonic lethality and failure of the epithelial component of the embryo to develop. Genes Dev. 1992;6:2235-47. (Pubitemid 23037390)
3. Charron J, Malynn BA, Fisher P, Stewart V, Jeannotte L, Goff SP, et al. Embryonic lethality in mice homozygous for a targeted disruption of the N-myc gene. Genes Dev. 1992;6: 2248-57. (Pubitemid 23037391)
4. Davis AC, Wims M, Spotts GD, Hann SR, Bradley A. A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. Genes Dev. 1993;7:671-82. (Pubitemid 23125266)
5. Knoepfler PS, Cheng PF, Eisenman RN. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev. 2002;16:2699-712.
6. Hatton BA, Knoepfler PS, Kenney AM, Rowitch DH, de Alboran IM, Olson JM, et al. N-myc is an essential downstream effector of Shh signaling during both normal and neoplastic cerebellar growth. Cancer Res. 2006;66:8655-61. (Pubitemid 44449181)
7. Zindy F, Knoepfler PS, Xie S, Sherr CJ, Eisenman RN, Roussel MF. N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development. Proc Natl Acad Sci USA. 2006;103:11579-83. (Pubitemid 44182494)
8. Wey A, Knoepfler PS. c-myc and N-myc promote active stem cell metabolism and cycling as architects of the developing brain. Oncotarget. 2010;1:120-30.
9. Fults D, Pedone C, Dai C, Holland EC. MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo. Neoplasia. 2002;4:32-9. (Pubitemid 34075888)
10. Eberhart CG, Kratz J, Wang Y, Summers K, Stearns D, Cohen K, et al. Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol. 2004;63:441-9. (Pubitemid 38669665)
11. Pfister S, Remke M, Benner A, Mendrzyk F, Toedt G, Felsberg J, et al. Outcome prediction in pediatric medullo-blastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. J Clin Oncol. 2009;27:1627-36.
12. Aldosari N, Bigner SH, Burger PC, Becker L, Kepner JL, Friedman HS, et al. MYCC and MYCN oncogene amplification in medulloblastoma. A fluorescence in situ hybridization study on paraffin sections from the Children's Oncology Group. Arch Pathol Lab Med. 2002;126:540-4. (Pubitemid 34477948)
13. Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M, et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell. 2008;14:135-45.
14. Brennan C, Momota H, Hambardzumyan D, Ozawa T, Tandon A, Pedraza A, et al. Glioblastoma subclasses can be defined by activity among signal transduction pathways and associated genomic alterations. PLoS One. 2009;4:e7752.
15. Perry A, Miller CR, Gujrati M, Scheithauer BW, Zambrano SC, Jost SC, et al. Malignant gliomas with primitive neuroectodermal tumor-like components: a clinico-pathologic and genetic study of 53 cases. Brain Pathol. 2009; 19:81-90.
16. Rouah E, Wilson DR, Armstrong DL, Darlington GJ. N-myc amplification and neuronal differentiation in human primitive neuroectodermal tumors of the central nervous system. Cancer Res. 1989;49:1797-801. (Pubitemid 19108407)
17. Browd SR, Kenney AM, Gottfried ON, Yoon JW, Walterhouse D, Pedone CA, et al. N-myc can substitute for insulin-like growth factor signaling in a mouse model of sonic hedgehog-induced medulloblastoma. Cancer Res. 2006; 66:2666-72.
18. Kessler JD, Hasegawa H, Brun SN, Yang ZJ, Dutton JW, Wang F, et al. N-myc alters the fate of preneoplastic cells in a mouse model of medulloblastoma. Genes Dev. 2009;23: 157-70.
19. Zindy F, Uziel T, Ayrault O, Calabrese C, Valentine M, Rehg JE, et al. Genetic alterations in mouse medulloblastomas and generation of tumors de novo from primary cerebellar granule neuron precursors. Cancer Res. 2007;67:2676-84. (Pubitemid 46548955)
20. Swartling FJ, Grimmer MR, Hackett CS, Northcott PA, Fan QW, Goldenberg DD, et al. Pleiotropic role for MYCN in medulloblastoma. Genes Dev. 2010;24:1059-72.
21. Momota H, Shih AH, Edgar MA, Holland EC. C-Myc and beta-catenin cooperate with loss of p53 to generate multiple members of the primitive neuroectodermal tumor family in mice. Oncogene. 2008;27:4392-401.
22. Lassman AB, Dai C, Fuller GN, Vickers AJ, Holland EC. Overexpression of c-MYC promotes an undifferentiated phenotype in cultured astrocytes and allows elevated Ras and Akt signaling to induce gliomas from GFAP-expressing cells in mice. Neuron Glia Biol. 2004;1:157-63.
23. Lee JS, Lee HJ, Moon BH, Song SH, Lee MO, Shim SH, et al. Generation of Cancerous neural stem cells forming glial tumor by oncogenic stimulation. Stem Cell Rev. 2011;Jul14Epub ahead of print.
24. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008;8:976-90.
25. Davis FG, McCarthy BJ, Berger MS. Centralized databases available for describing primary brain tumor incidence, survival, and treatment: Central Brain Tumor Registry of the United States; Surveillance, Epidemiology, and End Results; and National Cancer Data Base. Neuro Oncol. 1999;1:205-11.
26. Gilbertson RJ. Medulloblastoma: signalling a change in treatment. Lancet Oncol. 2004;5:209-18. (Pubitemid 38391216)
27. Eberhart CG, Burger PC. Anaplasia and grading in medul-loblastomas. Brain Pathol. 2003;13:376-85.
28. Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, et al. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol. 2006;24:1924-31. (Pubitemid 46638992)
29. Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, et al. Integrated genomics identifies five medul-loblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One. 2008; 3:e3088.
30. Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, et al. Integrative genomic analysis of medullo-blastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol. 2011;29:1424-30.
31. Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol. 2011;29: 1408-14.
32. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2011;[Epub ahead of print].
33. Clifford SC, Lusher ME, Lindsey JC, Langdon JA, Gilbertson RJ, Straughton D, et al. Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular sub-group of medulloblastomas associated with a favorable prognosis. Cell Cycle. 2006;5:2666-70.
34. Ellison DW, Dalton J, Kocak M, Nicholson SL, Fraga C, Neale G, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol. 2011;121:381-96.
35. Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS, Eden C, et al. Subtypes of medulloblastoma have distinct developmental origins. Nature. 2010;468:1095-9.
36. Fan X, Matsui W, Khaki L, Stearns D, Chun J, Li YM, et al. Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res. 2006;66: 7445-52. (Pubitemid 44289197)
37. Fouladi M, Stewart CF, Olson J, Wagner LM, Onar-Thomas A, Kocak M, et al. Phase I trial of MK-0752 in children with refractory CNS malignancies: A pediatric brain tumor consortium study. J Clin Oncol. 2011;29:3529-34.
38. Hatton BA, Villavicencio EH, Pritchard J, LeBlanc M, Hansen S, Ulrich M, et al. Notch signaling is not essential in sonic hedgehog-activated medulloblastoma. Oncogene. 2010;29:3865-72.
39. Julian E, Dave RK, Robson JP, Hallahan AR, Wainwright BJ. Canonical Notch signaling is not required for the growth of Hedgehog pathway-induced medulloblastoma. Oncogene. 2010;29:3465-76.
40. Wu X, Northcott PA, Croul S, Taylor MD. Mouse models of medulloblastoma. Chin J Cancer. 2011;30:442-9.
41. Goodrich LV, Milenkovic L, Higgins KM, Scott MP. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science. 1997;277:1109-13. (Pubitemid 27371635)
42. Eberhart CG, Kratz JE, Schuster A, Goldthwaite P, Cohen KJ, Perlman EJ, et al. Comparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas. Brain Pathol. 2002;12:36-44. (Pubitemid 33131360)
43. Stearns D, Chaudhry A, Abel TW, Burger PC, Dang CV, Eberhart CG. C-myc overexpression causes anaplasia in medulloblastoma. Cancer Res. 2006;66:673-81. (Pubitemid 43165929)
44. Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002;415:436-42. (Pubitemid 34100955)
45. Kenney AM, Cole MD, Rowitch DH. Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development. 2003; 130:15-28. (Pubitemid 36113940)
46. Korshunov A, Remke M, Kool M, Hielscher T, Northcott PA, Williamson D, et al. Biological and clinical heterogeneity of MYCN-amplified medulloblastoma. Acta Neuropathol. 2011;[Epub ahead of print].
47. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97-109. (Pubitemid 47103521)
48. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359:492-507.
49. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459-66.
50. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006;9:157-73. (Pubitemid 43357943)
51. TCGA research network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061-8.
52. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98-110.
53. Herms JW, von Loewenich FD, Behnke J, Markakis E, Kretzschmar HA. C-myc oncogene family expression in glio-blastoma and survival. Surg Neurol. 1999;51:536-42. (Pubitemid 29218069)
54. Hui AB, Lo KW, Yin XL, Poon WS, Ng HK. Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization. Lab Invest. 2001;81:717-23. (Pubitemid 32466534)
55. Faria MH, Khayat AS, Burbano RR, Rabenhorst SH. C-MYC amplification and expression in astrocytic tumors. Acta Neuropathol. 2008;116:87-95.
56. Hodgson JG, Yeh RF, Ray A, Wang NJ, Smirnov I, Yu M, et al. Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts. Neuro Oncol. 2009;11:477-87.
57. Ho JS, Ma W, Mao DY, Benchimol S. p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol. 2005;25:7423-31. (Pubitemid 41170106)
58. Broaddus WC, Chen ZJ, Prabhu SS, Loudon WG, Gillies GT, Phillips LL, et al. Antiproliferative effect of c-myc antisense phosphorothioate oligodeoxynucleotides in malignant glioma cells. Neurosurgery. 1997;41:908-15. (Pubitemid 27422119)
59. Wang J, Wang H, Li Z, Wu Q, Lathia JD, McLendon RE, et al. c-Myc is required for maintenance of glioma cancer stem cells. PLoS One. 2008;3:e3769.
60. Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen AJ, et al. p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature. 2008;455:1129-33.
61. Amati B, Brooks MW, Levy N, Littlewood TD, Evan GI, Land H. Oncogenic activity of the c-Myc protein requires dimerization with Max. Cell. 1993;72:233-45. (Pubitemid 23044938)
62. Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN, Weintraub H. Sequence-specific DNA binding by the c-Myc protein. Science. 1990;250:1149-51. (Pubitemid 120031826)
63. Papoulas O, Williams NG, Kingston RE. DNA binding activities of c-Myc purified from eukaryotic cells. J Biol Chem. 1992;267:10470-80.
64. Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, et al. Repression of p15INK4b expression by Myc through association with Miz-1. Nat Cell Biol. 2001; 3:392-9. (Pubitemid 32288447)
65. Herold S, Herkert B, Eilers M. Facilitating replication under stress: an oncogenic function of MYC? Nat Rev Cancer. 2009; 9:441-4.
66. Wu S, Cetinkaya C, Munoz-Alonso MJ, von der Lehr N, Bahram F, Beuger V, et al. Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter. Oncogene. 2003;22:351-60. (Pubitemid 36194331)
67. Patel JH, Loboda AP, Showe MK, Showe LC, McMahon SB. Analysis of genomic targets reveals complex functions of MYC. Nat Rev Cancer. 2004;4:562-8. (Pubitemid 38868625)
68. Hatton KS, Mahon K, Chin L, Chiu FC, Lee HW, Peng D, et al. Expression and activity of L-Myc in normal mouse development. Mol Cell Biol. 1996;16:1794-804. (Pubitemid 26098633)
69. Kenney AM, Widlund HR, Rowitch DH. Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors. Development. 2004;131:217-28. (Pubitemid 38111428)
70. Sjostrom SK, Finn G, Hahn WC, Rowitch DH, Kenney AM. The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors. Dev Cell. 2005;9:327-38. (Pubitemid 41235803)
71. Benassi B, Fanciulli M, Fiorentino F, Porrello A, Chiorino G, Loda M, et al. c-Myc phosphorylation is required for cellular response to oxidative stress. Mol Cell. 2006;21:509-19. (Pubitemid 43228006)
72. Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008;26:101-6.
73. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663-76. (Pubitemid 44233629)
74. Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008;451:141-6.
75. Kim SU, Park IH, Kim TH, Kim KS, Choi HB, Hong SH, et al. Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson disease. Neuropathology. 2006;26: 129-40.
76. Villa A, Snyder EY, Vescovi A, Martinez-Serrano A. Establishment and properties of a growth factor-dependent, perpetual neural stem cell line from the human CNS. Exp Neurol. 2000;161:67-84. (Pubitemid 30136530)
77. Queva C, Hurlin PJ, Foley KP, Eisenman RN. Sequential expression of the MAD family of transcriptional repressors during differentiation and development. Oncogene. 1998; 16:967-77. (Pubitemid 28107934)
78. Schreiber-Agus N, DePinho RA. Repression by the Mad (Mxi1)-Sin3 complex. Bioessays. 1998;20:808-18.
79. Wechsler DS, Shelly CA, Petroff CA, Dang CV. MXI1, a putative tumor suppressor gene, suppresses growth of human glioblastoma cells. Cancer Res. 1997;57:4905-12. (Pubitemid 27469001)
80. Manni I, Tunici P, Cirenei N, Albarosa R, Colombo BM, Roz L, et al. Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression. Br J Cancer. 2002;86:477-84. (Pubitemid 34185136)
81. Hann SR, Eisenman RN. Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol. 1984;4:2486-97. (Pubitemid 15212264)
82. Pulverer BJ, Fisher C, Vousden K, Littlewood T, Evan G, Woodgett JR. Site-specific modulation of c-Myc cotransfor-mation by residues phosphorylated in vivo. Oncogene. 1994; 9:59-70. (Pubitemid 24020934)
83. Sears R, Nuckolls F, Haura E, Taya Y, Tamai K, Nevins JR. Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev. 2000;14:2501-14.
84. Gregory MA, Qi Y, Hann SR. Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization. J Biol Chem. 2003;278:51606-12. (Pubitemid 38020405)
85. Flinn EM, Busch CM, Wright AP. Myc boxes, which are conserved in myc family proteins, are signals for protein degradation via the proteasome. Mol Cell Biol. 1998;18: 5961-9. (Pubitemid 28450547)
86. Salghetti SE, Kim SY, Tansey WP. Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. EMBO J. 1999;18:717-26. (Pubitemid 29057256)
87. Yeh E, Cunningham M, Arnold H, Chasse D, Monteith T, Ivaldi G, et al. A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol. 2004;6:308-18. (Pubitemid 38584820)
88. Schrader EK, Harstad KG, Matouschek A. Targeting proteins for degradation. Nat Chem Biol. 2009;5:815-22.
89. Thrower JS, Hoffman L, Rechsteiner M, Pickart CM. Recognition of the polyubiquitin proteolytic signal. EMBO J. 2000; 19:94-102. (Pubitemid 30009229)
90. Blancato J, Singh B, Liu A, Liao DJ, Dickson RB. Correlation of amplification and overexpression of the c-myc oncogene in high-grade breast cancer: FISH, in situ hybridisation and immunohistochemical analyses. Br J Cancer. 2004;90: 1612-19. (Pubitemid 38648247)
91. Pollack JR, Sorlie T, Perou CM, Rees CA, Jeffrey SS, Lonning PE, et al. Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc Natl Acad Sci USA. 2002;99:12963-8.
92. Vita M, Henriksson M. The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol. 2006;16: 318-30. (Pubitemid 44311040)
93. Thomas LR, Tansey WP. Proteolytic control of the onco-protein transcription factor Myc. Adv Cancer Res. 2011;110: 77-106.
94. Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H, et al. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 2004;23:2116-25. (Pubitemid 38737738)
95. O'Neil J, Look AT. Mechanisms of transcription factor deregulation in lymphoid cell transformation. Oncogene. 2007;26: 6838-49. (Pubitemid 47585107)
96. Hoeck JD, Jandke A, Blake SM, Nye E, Spencer-Dene B, Brandner S, et al. Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun. Nat Neurosci. 2010;13:1365-72.
97. Jandke A, Da Costa C, Sancho R, Nye E, Spencer-Dene B, Behrens A. The F-box protein Fbw7 is required for cerebellar development. Dev Biol. 2011;358:201-12.
98. Kim SY, Herbst A, Tworkowski KA, Salghetti SE, Tansey WP. Skp2 regulates Myc protein stability and activity. Mol Cell. 2003;11:1177-88. (Pubitemid 36645138)
99. Gstaiger M, Jordan R, Lim M, Catzavelos C, Mestan J, Slingerland J, et al. Skp2 is oncogenic and overexpressed in human cancers. Proc Natl Acad Sci USA. 2001;98:5043-8. (Pubitemid 32397079)
100. von der Lehr N, Johansson S, Wu S, Bahram F, Castell A, Cetinkaya C, et al. The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Mol Cell. 2003;11:1189-200. (Pubitemid 36645139)
101. Popov N, Wanzel M, Madiredjo M, Zhang D, Beijersbergen R, Bernards R, et al. The ubiquitin-specific protease USP28 is required for MYC stability. Nat Cell Biol. 2007;9:765-74. (Pubitemid 47019463)
102. Schwamborn JC, Berezikov E, Knoblich JA. The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell. 2009;136: 913-25.
103. Papas TS, Lautenberger JA. Sequence curiosity in v-myc oncogene. Nature. 1985;318:237. (Pubitemid 16206728)
104. Hoang AT, Lutterbach B, Lewis BC, Yano T, Chou TY, Barrett JF, et al. A link between increased transforming activity of lymphoma-derived MYC mutant alleles, their defective regulation by p107, and altered phosphorylation of the c-Myc transactivation domain. Mol Cell Biol. 1995;15: 4031-42.
105. Bamford S, Dawson E, Forbes S, Clements J, Pettett R, Dogan A, et al. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer. 2004;91: 355-8. (Pubitemid 39037083)
106. Land H, Parada LF, Weinberg RA. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983;304:596-602. (Pubitemid 13035496)
107. Foroni C, Galli R, Cipelletti B, Caumo A, Alberti S, Fiocco R, et al. Resilience to transformation and inherent genetic and functional stability of adult neural stem cells ex vivo. Cancer Res. 2007;67:3725-33. (Pubitemid 46762158)
108. Forbes SA, Bhamra G, Bamford S, Dawson E, Kok C, Clements J, et al. The Catalogue of Somatic Mutations in Cancer (COSMIC). Curr Protoc Hum Genet. 2008;Chapter 10:Unit 10.11.
109. Hydbring P, Bahram F, Su Y, Tronnersjo S, Hogstrand K, von der Lehr N, et al. Phosphorylation by Cdk2 is required for Myc to repress Ras-induced senescence in cotransforma-tion. Proc Natl Acad Sci USA. 2010;107:58-63.
110. Campaner S, Doni M, Hydbring P, Verrecchia A, Bianchi L, Sardella D, et al. Cdk2 suppresses cellular senescence induced by the c-myc oncogene. Nat Cell Biol. 2010;12: 54-9; sup pp 1-14.
111. Johansson FK, Brodd J, Eklof C, Ferletta M, Hesselager G, Tiger CF, et al. Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging. Proc Natl Acad Sci USA. 2004;101:11334-7. (Pubitemid 39038347)
112. Johansson Swartling F. Identifying candidate genes involved in brain tumor formation. Ups J Med Sci. 2008;113:1-38.
113. Collier LS, Carlson CM, Ravimohan S, Dupuy AJ, Largaespada DA. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature. 2005;436:272-6. (Pubitemid 41021279)
114. Dupuy AJ, Akagi K, Largaespada DA, Copeland NG, Jenkins NA. Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature. 2005; 436:221-6. (Pubitemid 41021267)
115. Bender AM, Collier LS, Rodriguez FJ, Tieu C, Larson JD, Halder C, et al. Sleeping beauty-mediated somatic muta-genesis implicates CSF1 in the formation of high-grade astrocytomas. Cancer Res. 2010;70:3557-65.
116. Collier LS, Adams DJ, Hackett CS, Bendzick LE, Akagi K, Davies MN, et al. Whole-body sleeping beauty mutagenesis can cause penetrant leukemia/lymphoma and rare high-grade glioma without associated embryonic lethality. Cancer Res. 2009;69:8429-37.
117. Felsher DW. MYC inactivation elicits oncogene addiction through both tumor cell-intrinsic and host-dependent mechanisms. Genes Cancer. 2010;1:597-604.
118. Gustafson WC, Weiss WA. Myc proteins as therapeutic targets. Oncogene. 2010;29:1249-59.
119. Westermark UK, Wilhelm M, Frenzel A, Henriksson MA. The MYCN oncogene and differentiation in neuroblastoma. Semin Cancer Biol. 2011;21:256-66.
120. Yin X, Giap C, Lazo JS, Prochownik EV. Low molecular weight inhibitors of Myc-Max interaction and function. Oncogene. 2003;22:6151-9. (Pubitemid 37281644)
121. Huang MJ, Cheng YC, Liu CR, Lin S, Liu HE. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp Hematol. 2006;34:1480-9. (Pubitemid 44548118)
122. Wang H, Hammoudeh DI, Follis AV, Reese BE, Lazo JS, Metallo SJ, et al. Improved low molecular weight Myc-Max inhibitors. Mol Cancer Ther. 2007;6:2399-408. (Pubitemid 47480405)
123. Chen J, Willingham T, Margraf LR, Schreiber-Agus N, DePinho RA, Nisen PD. Effects of the MYC oncogene antagonist, MAD, on proliferation, cell cycling and the malignant phenotype of human brain tumour cells. Nat Med. 1995;1:638-43.
124. Shalaby T, von Bueren AO, Hurlimann ML, Fiaschetti G, Castelletti D, Masayuki T, et al. Disabling c-Myc in childhood medulloblastoma and atypical teratoid/rhabdoid tumor cells by the potent G-quadruplex interactive agent S2T1-6OTD. Mol Cancer Ther. 2010;9:167-79.
125. van Riggelen J, Yetil A, Felsher DW. MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer. 2010;10:301-9.
126. SchlosserI, HolzelM, MurnseerM, BurtscherH, WeidleUH, Eick D. A role for c-Myc in the regulation of ribosomal RNA processing. Nucleic Acids Res. 2003;31:6148-56.
127. Boon K, Caron HN, van Asperen R, Valentijn L, Hermus MC, van Sluis P, et al. N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis. EMBO J. 2001;20:1383-93. (Pubitemid 32233978)
128. Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, et al. c-Myc regulates transcriptional pause release. Cell. 2010;141:432-45.
129. Knoepfler PS, Zhang XY, Cheng PF, Gafken PR, McMahon SB, Eisenman RN. Myc influences global chromatin structure. EMBO J. 2006;25:2723-34. (Pubitemid 43980380)
130. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146:904-17.
131. Marampon F, Ciccarelli C, Zani BM. Down-regulation of c-Myc following MEK/ERK inhibition halts the expression of malignant phenotype in rhabdomyosarcoma and in non muscle-derived human tumors. Mol Cancer. 2006;5:31.
132. Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell. 2008;14:123-34.
133. Hydbring P, Larsson LG. Tipping the balance: Cdk2 enables Myc to suppress senescence. Cancer Res. 2010;70:6687-91.
134. Goga A, Yang D, Tward AD, Morgan DO, Bishop JM. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat Med. 2007;13:820-7. (Pubitemid 47038193)
135. Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, et al. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992;69:119-28.
136. De Salvo M, Maresca G, D'Agnano I, Marchese R, Stigliano A, Gagliassi R, et al. Temozolomide induced c-Myc-mediated apoptosis via Akt signalling in MGMT expressing glioblastoma cells. Int J Radiat Biol. 2011;87: 518-33.
137. Gera JF, Mellinghoff IK, Shi Y, Rettig MB, Tran C, Hsu JH, et al. AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression. J Biol Chem. 2004;279: 2737-46. (Pubitemid 38114263)
138. Peterson RT, Desai BN, Hardwick JS, Schreiber SL. Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein. Proc Natl Acad Sci USA. 1999;96:4438-42. (Pubitemid 29190354)
139. Chesler L, Schlieve C, Goldenberg DD, Kenney A, Kim G, McMillan A, et al. Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks malignant progression in neuroblastoma. Cancer Res. 2006;66: 8139-46. (Pubitemid 44299181)
140. Johnsen JI, Segerstrom L, Orrego A, Elfman L, Henriksson M, Kagedal B, et al. Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo. Oncogene. 2008;27:2910-22. (Pubitemid 351620441)
141. Fan QW, Knight ZA, Goldenberg DD, Yu W, Mostov KE, Stokoe D, et al. A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell. 2006; 9:341-9. (Pubitemid 43668732)
142. Baryawno N, Sveinbjornsson B, Eksborg S, Chen CS, Kogner P, Johnsen JI. Small-molecule inhibitors of phos-phatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-cate-nin pathway cross-talk and suppress medulloblastoma growth. Cancer Res. 2010;70:266-76.
143. Heine VM, Priller M, Ling J, Rowitch DH, Schuller U. Dexamethasone destabilizes Nmyc to inhibit the growth of hedgehog-associated medulloblastoma. Cancer Res. 2010; 70:5220-5.
144. Hoeller D, Dikic I. Targeting the ubiquitin system in cancer therapy. Nature. 2009;458:438-44.