MYCN

Summary

Gene Symbol: MYCN
Description: MYCN proto-oncogene, bHLH transcription factor
Alias: MODED, N-myc, NMYC, ODED, bHLHe37, N-myc proto-oncogene protein, class E basic helix-loop-helix protein 37, neuroblastoma MYC oncogene, neuroblastoma-derived v-myc avian myelocytomatosis viral related oncogene, oncogene NMYC, v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog
Species: human
Products:     MYCN

Top Publications

  1. Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12:247-56 pubmed publisher
    ..Expression of miR-9 is activated by MYC and MYCN, both of which directly bind to the mir-9-3 locus...
  2. Hatzi E, Murphy C, Zoephel A, Ahorn H, Tontsch U, Bamberger A, et al. N-myc oncogene overexpression down-regulates leukemia inhibitory factor in neuroblastoma. Eur J Biochem. 2002;269:3732-41 pubmed
    ..Our data shed light on the mechanisms by which N-myc oncogene amplification enhances the malignant phenotype in neuroblastoma. ..
  3. Corvetta D, Chayka O, Gherardi S, D Acunto C, Cantilena S, Valli E, et al. Physical interaction between MYCN oncogene and polycomb repressive complex 2 (PRC2) in neuroblastoma: functional and therapeutic implications. J Biol Chem. 2013;288:8332-41 pubmed publisher
    CLU (clusterin) is a tumor suppressor gene that we have previously shown to be negatively modulated by the MYCN proto-oncogene, but the mechanism of repression was unclear...
  4. Brockmann M, Poon E, Berry T, Carstensen A, Deubzer H, Rycak L, et al. Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell. 2013;24:75-89 pubmed publisher
    Amplification of MYCN is a driver mutation in a subset of human neuroendocrine tumors, including neuroblastoma. No small molecules that target N-Myc, the protein encoded by MYCN, are clinically available...
  5. Stanton L, Schwab M, Bishop J. Nucleotide sequence of the human N-myc gene. Proc Natl Acad Sci U S A. 1986;83:1772-6 pubmed
    ..The resemblance between the proteins encoded by N-myc and c-myc sustains previous suspicions that the genes encode related functions. ..
  6. Gamble L, Kees U, Tweddle D, Lunec J. MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63. Oncogene. 2012;31:752-63 pubmed publisher
    b>MYCN amplification is a major biomarker of poor prognosis, occurring in 25-30% of neuroblastomas. MYCN has contradictory roles in promoting cell growth and sensitizing cells to apoptosis...
  7. Huang R, Cheung N, Vider J, Cheung I, Gerald W, Tickoo S, et al. MYCN and MYC regulate tumor proliferation and tumorigenesis directly through BMI1 in human neuroblastomas. FASEB J. 2011;25:4138-49 pubmed publisher
    ..Using microarray and immunohistochemical analysis, we show that BMI1 expression correlated with MYCN levels in MYCN-amplified human neuroblastomas, and with MYC levels in the MYCN-nonamplified group...
  8. Cotterman R, Jin V, Krig S, Lemen J, Wey A, Farnham P, et al. N-Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factor. Cancer Res. 2008;68:9654-62 pubmed publisher
    ..These findings support a new dual model for Myc chromatin function with important implications for the role of Myc in cancer and stem cell biology, including that of induced pluripotent stem cells. ..
  9. Lovén J, Zinin N, Wahlström T, Müller I, Brodin P, Fredlund E, et al. MYCN-regulated microRNAs repress estrogen receptor-alpha (ESR1) expression and neuronal differentiation in human neuroblastoma. Proc Natl Acad Sci U S A. 2010;107:1553-8 pubmed publisher
    b>MYCN, a proto-oncogene normally expressed in the migrating neural crest, is in its amplified state a key factor in the genesis of human neuroblastoma (NB)...

More Information

Publications86

  1. Chesler L, Schlieve C, Goldenberg D, 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 pubmed
    Amplification of MYCN occurs commonly in neuroblastoma...
  2. Wartiovaara K, Barnabe Heider F, Miller F, Kaplan D. N-myc promotes survival and induces S-phase entry of postmitotic sympathetic neurons. J Neurosci. 2002;22:815-24 pubmed
    ..Thus, N-myc both selectively causes sympathetic neurons to reenter the cell cycle and protects them from apoptosis, potentially contributing to their transformation to NBs. ..
  3. Tee A, Marshall G, Liu P, Xu N, Haber M, Norris M, et al. Opposing effects of two tissue transglutaminase protein isoforms in neuroblastoma cell differentiation. J Biol Chem. 2010;285:3561-7 pubmed publisher
  4. Armstrong B, Krystal G. Isolation and characterization of complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc. Cell Growth Differ. 1992;3:385-90 pubmed
    ..This coregulation suggests that their protein products may be functionally interrelated during normal development and oncogenesis. ..
  5. Chen L, Iraci N, Gherardi S, Gamble L, Wood K, Perini G, et al. p53 is a direct transcriptional target of MYCN in neuroblastoma. Cancer Res. 2010;70:1377-88 pubmed publisher
    b>MYCN amplification occurs in approximately 25% of neuroblastomas, where it is associated with rapid tumor progression and poor prognosis. MYCN plays a paradoxical role in driving cellular proliferation and inducing apoptosis...
  6. Gupta A, Williams B, Hanash S, Rawwas J. Cellular retinoic acid-binding protein II is a direct transcriptional target of MycN in neuroblastoma. Cancer Res. 2006;66:8100-8 pubmed
    Neuroblastoma is a heterogeneous disease in which 22% of tumors show MycN oncogene amplification and are associated with poor clinical outcome...
  7. Bell E, Premkumar R, Carr J, Lu X, Lovat P, Kees U, et al. The role of MYCN in the failure of MYCN amplified neuroblastoma cell lines to G1 arrest after DNA damage. Cell Cycle. 2006;5:2639-47 pubmed
    We previously reported that 3 p53 wild type (wt) MYCN amplified (MNA) neuroblastoma cell lines failed to G1 arrest after DNA damage despite induction of p53, p21(WAF1) and MDM2. We hypothesised that this was due to high MYCN expression...
  8. Zhu S, Lee J, Guo F, Shin J, Perez Atayde A, Kutok J, et al. Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell. 2012;21:362-73 pubmed publisher
    Amplification of the MYCN oncogene in childhood neuroblastoma is often accompanied by mutational activation of ALK (anaplastic lymphoma kinase), suggesting their pathogenic cooperation...
  9. Stock C, Bozsaky E, Watzinger F, Poetschger U, Orel L, Lion T, et al. Genes proximal and distal to MYCN are highly expressed in human neuroblastoma as visualized by comparative expressed sequence hybridization. Am J Pathol. 2008;172:203-14 pubmed publisher
    b>MYCN amplification is associated with poor prognosis in neuroblastoma disease...
  10. Torres J, Regan P, Edo R, Leonhardt P, Jeng E, Rappaport E, et al. Biological effects of induced MYCN hyper-expression in MYCN-amplified neuroblastomas. Int J Oncol. 2010;37:983-91 pubmed
    ..The tumor exhibits two different phenotypes: favorable and unfavorable. MYCN amplification is associated with rapid tumor progression and the worst neuroblastoma disease outcome...
  11. Marshall G, Gherardi S, Xu N, Neiron Z, Trahair T, Scarlett C, et al. Transcriptional upregulation of histone deacetylase 2 promotes Myc-induced oncogenic effects. Oncogene. 2010;29:5957-68 pubmed publisher
  12. Shohet J, Hicks M, Plon S, Burlingame S, Stuart S, Chen S, et al. Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer Res. 2002;62:1123-8 pubmed
    The MYCN oncogene is amplified in approximately 25% of neuroblastoma tumors and is the most significant negative prognostic factor. The direct transcriptional targets of MYCN in MYCN-amplified tumors have not been defined...
  13. Ikegaki N, Hicks S, Regan P, Jacobs J, Jumbo A, Leonhardt P, et al. S(+)-ibuprofen destabilizes MYC/MYCN and AKT, increases p53 expression, and induces unfolded protein response and favorable phenotype in neuroblastoma cell lines. Int J Oncol. 2014;44:35-43 pubmed publisher
    ..The survival rate of children with unfavorable neuroblastoma remains low among all childhood cancers. MYCN and MYC play a crucial role in determining the malignancy of unfavorable neuroblastomas, whereas high-level ..
  14. Puissant A, Frumm S, Alexe G, Bassil C, Qi J, Chanthery Y, et al. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013;3:308-23 pubmed publisher
    ..Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition...
  15. Schleiermacher G, Michon J, Ribeiro A, Pierron G, Mosseri V, Rubie H, et al. Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study). Br J Cancer. 2011;105:1940-8 pubmed publisher
    ..In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European ..
  16. Strieder V, Lutz W. E2F proteins regulate MYCN expression in neuroblastomas. J Biol Chem. 2003;278:2983-9 pubmed
    Amplification of the MYCN gene, resulting in overexpression of MYCN, distinguishes a subset of neuroblastomas with poor prognosis. The transcription factors driving MYCN expression in neuroblastomas are unknown...
  17. Chayka O, Corvetta D, Dews M, Caccamo A, Piotrowska I, Santilli G, et al. Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas. J Natl Cancer Inst. 2009;101:663-77 pubmed publisher
    ..expression of microRNAs in the miR-17-92 cluster by real-time reverse transcription-polymerase chain reaction in MYCN-transfected SH-SY5Y and SH-EP cells and inhibited expression by transfection with microRNA antisense ..
  18. Bray I, Bryan K, Prenter S, Buckley P, Foley N, Murphy D, et al. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival. PLoS ONE. 2009;4:e7850 pubmed publisher
    ..Thirty-seven miRNAs were significantly over- or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor ..
  19. Defferrari R, Tonini G, Conte M, Papio F, Sementa A, Valent A, et al. Concomitant DDX1 and MYCN gain in neuroblastoma. Cancer Lett. 2007;256:56-63 pubmed
    DDX1, a gene mapping to the 2p24 region, has been observed to be co-amplified with MYCN in neuroblastoma. Co-amplification of the DDX1 gene is a consequence of the short physical distance between the two genes...
  20. Krystal G, Armstrong B, Battey J. N-myc mRNA forms an RNA-RNA duplex with endogenous antisense transcripts. Mol Cell Biol. 1990;10:4180-91 pubmed
  21. Giannini G, Cerignoli F, Mellone M, Massimi I, Ambrosi C, Rinaldi C, et al. High mobility group A1 is a molecular target for MYCN in human neuroblastoma. Cancer Res. 2005;65:8308-16 pubmed
    ..On retinoic acid (RA) treatment of MYCN-amplified neuroblastoma cell lines, HMGA1 decreases with a kinetics that strictly follows MYCN repression...
  22. Stanton L, Bishop J. Alternative processing of RNA transcribed from NMYC. Mol Cell Biol. 1987;7:4266-72 pubmed
    b>NMYC is a gene whose amplification and overexpression have been implicated in the generation of certain human malignancies. Little is known of how the expression of NMYC is normally controlled...
  23. Hansford L, Thomas W, Keating J, Burkhart C, Peaston A, Norris M, et al. Mechanisms of embryonal tumor initiation: distinct roles for MycN expression and MYCN amplification. Proc Natl Acad Sci U S A. 2004;101:12664-9 pubmed
    ..One tumorigenic factor in the embryonal childhood tumor neuroblastoma is the MYCN protooncogene...
  24. Muth D, Ghazaryan S, Eckerle I, Beckett E, Pöhler C, Batzler J, et al. Transcriptional repression of SKP2 is impaired in MYCN-amplified neuroblastoma. Cancer Res. 2010;70:3791-802 pubmed publisher
    ..The highest SKP2 levels are found in neuroblastomas with amplified MYCN. Accordingly, we found 5.5-fold (range, 2-9.5) higher SKP2 core promoter activity in MYCN-amplified cells...
  25. Rushlow D, Mol B, Kennett J, Yee S, Pajovic S, Thériault B, et al. Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies. Lancet Oncol. 2013;14:327-34 pubmed publisher
    ..15 of the 29 RB1(+/+) tumours had high-level MYCN oncogene amplification (28-121 copies; RB1(+/+)MYCN(A)), whereas none of 93 RB1(-/-) primary tumours tested showed ..
  26. Haug B, Henriksen J, Buechner J, Geerts D, Tømte E, Kogner P, et al. MYCN-regulated miRNA-92 inhibits secretion of the tumor suppressor DICKKOPF-3 (DKK3) in neuroblastoma. Carcinogenesis. 2011;32:1005-12 pubmed publisher
    The MYCN oncogene is frequently amplified in neuroblastoma. It is one of the most consistent markers of bad prognosis for this disease. Dickkopf-3 (DKK3) is a secreted protein of the DKK family of Wnt regulators...
  27. Schönherr C, Ruuth K, Kamaraj S, Wang C, Yang H, Combaret V, et al. Anaplastic Lymphoma Kinase (ALK) regulates initiation of transcription of MYCN in neuroblastoma cells. Oncogene. 2012;31:5193-200 pubmed publisher
    ..sympathetic nervous system and a disease with several different chromosomal gains and losses, which include MYCN-amplified neuroblastoma on chromosome 2, deletions of parts of the chromosomes 1p and 11q, gain of parts of 17q and ..
  28. Cotterman R, Knoepfler P. N-Myc regulates expression of pluripotency genes in neuroblastoma including lif, klf2, klf4, and lin28b. PLoS ONE. 2009;4:e5799 pubmed publisher
    ..They also suggest mechanisms by which Myc proteins more generally contribute to maintenance of pluripotency and self-renewal of ESC as well as to iPSC formation. ..
  29. Gustafson W, Meyerowitz J, Nekritz E, Chen J, Benes C, Charron E, et al. Drugging MYCN through an allosteric transition in Aurora kinase A. Cancer Cell. 2014;26:414-427 pubmed publisher
    ..Proteolytic degradation of MYCN protein is regulated in part by a kinase-independent function of Aurora A...
  30. Schwab M, Varmus H, Bishop J, Grzeschik K, Naylor S, Sakaguchi A, et al. Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc. Nature. 1984;308:288-91 pubmed
  31. Marcelis C, Hol F, Graham G, Rieu P, Kellermayer R, Meijer R, et al. Genotype-phenotype correlations in MYCN-related Feingold syndrome. Hum Mutat. 2008;29:1125-32 pubmed publisher
    ..FS is caused by germline mutations in or deletions of the MYCN gene...
  32. Brodeur G, Seeger R, Schwab M, Varmus H, Bishop J. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984;224:1121-4 pubmed
    ..Furthermore, N-myc amplification is highly correlated with advanced stages of disease (P less than 0.001) and with the ability to grow in vitro as an established cell line, both of which are associated with a poor prognosis. ..
  33. Alaminos M, Mora J, Cheung N, Smith A, Qin J, Chen L, et al. Genome-wide analysis of gene expression associated with MYCN in human neuroblastoma. Cancer Res. 2003;63:4538-46 pubmed
    Molecular mechanisms through which MYCN expression contributes to the malignant phenotype of neuroblastoma are unknown...
  34. Wan T, Ma E, Chan G, Chan L. Investigation of MYCN status in neuroblastoma by fluorescence in situ hybridization. Int J Mol Med. 2004;14:981-7 pubmed
    ..We investigated 12 neuroblastoma patients for MYCN amplification and chromosome 2 aneusomy by fluorescence in situ hybridization (FISH) and results were correlated ..
  35. Westermann F, Muth D, Benner A, Bauer T, Henrich K, Oberthuer A, et al. Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas. Genome Biol. 2008;9:R150 pubmed publisher
    Amplified MYCN oncogene resulting in deregulated MYCN transcriptional activity is observed in 20% of neuroblastomas and identifies a highly aggressive subtype...
  36. Martins R, Zindy F, Donovan S, Zhang J, Pounds S, Wey A, et al. N-myc coordinates retinal growth with eye size during mouse development. Genes Dev. 2008;22:179-93 pubmed publisher
    ..We propose that N-myc lies upstream of the cell cycle machinery in the developing mouse retina and thus coordinates the growth of both the retina and eye through extrinsic cues. ..
  37. Blumrich A, Zapatka M, Brueckner L, Zheglo D, Schwab M, Savelyeva L. The FRA2C common fragile site maps to the borders of MYCN amplicons in neuroblastoma and is associated with gross chromosomal rearrangements in different cancers. Hum Mol Genet. 2011;20:1488-501 pubmed publisher
    ..3 and 2p24.2, respectively. Both cFS are separated by a 2.8 Mb non-fragile region containing MYCN. Fine-tiling array comparative genomic hybridization of MYCN amplicons from neuroblastoma (NB) cell lines and ..
  38. Ibson J, Rabbitts P. Sequence of a germ-line N-myc gene and amplification as a mechanism of activation. Oncogene. 1988;2:399-402 pubmed
  39. Ramsay G, Stanton L, Schwab M, Bishop J. Human proto-oncogene N-myc encodes nuclear proteins that bind DNA. Mol Cell Biol. 1986;6:4450-7 pubmed
    ..Our findings sustain the view that inordinate expression of N-myc may contribute to the genesis of several different human tumors...
  40. Liu P, Xu N, Malyukova A, Scarlett C, Sun Y, Zhang X, et al. The histone deacetylase SIRT2 stabilizes Myc oncoproteins. Cell Death Differ. 2013;20:503-14 pubmed publisher
    ..Our data reveal a novel pathway critical for Myc oncoprotein stability, and provide important evidences for potential application of SIRT2 inhibitors for the prevention and therapy of Myc-induced malignancies. ..
  41. Fieuw A, Kumps C, Schramm A, Pattyn F, Menten B, Antonacci F, et al. Identification of a novel recurrent 1q42.2-1qter deletion in high risk MYCN single copy 11q deleted neuroblastomas. Int J Cancer. 2012;130:2599-606 pubmed publisher
    ..The majority of all detected 1q deletions was found in high risk 11q deleted tumors without MYCN amplification (Fisher exact test p = 5.61 × 10(-5) )...
  42. Moreau L, McGrady P, London W, Shimada H, Cohn S, Maris J, et al. Does MYCN amplification manifested as homogeneously staining regions at diagnosis predict a worse outcome in children with neuroblastoma? A Children's Oncology Group study. Clin Cancer Res. 2006;12:5693-7 pubmed
    b>MYCN amplification in neuroblastoma tumor cells is manifested primarily as double minutes (dmins), whereas in cell lines it often appears in the form of homogeneously staining regions (HSR), suggesting that HSRs are associated with a more ..
  43. Amente S, Gargano B, Diolaiti D, Della Valle G, Lania L, Majello B. p14ARF interacts with N-Myc and inhibits its transcriptional activity. FEBS Lett. 2007;581:821-5 pubmed
    ..Finally, we determine that the N-terminal region of the p14(ARF) protein is involved in binding to c-Myc and N-Myc proteins. ..
  44. Mestdagh P, Fredlund E, Pattyn F, Schulte J, Muth D, Vermeulen J, et al. MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors. Oncogene. 2010;29:1394-404 pubmed publisher
    ..Using neuroblastoma as a tumor model, we established a microRNA (miRNA) signature for activated MYCN/c-MYC signaling in two independent primary neuroblastoma tumor cohorts and provide evidence that c-MYC and MYCN ..
  45. Chen Z, Lin Y, Barbieri E, Burlingame S, Hicks J, Ludwig A, et al. Mdm2 deficiency suppresses MYCN-Driven neuroblastoma tumorigenesis in vivo. Neoplasia. 2009;11:753-62 pubmed
    ..Amplification of the MYCN oncogene correlates with the most clinically aggressive form of the cancer, and MDM2, a primary inhibitor of the ..
  46. Schneiderman J, London W, Brodeur G, Castleberry R, Look A, Cohn S. Clinical significance of MYCN amplification and ploidy in favorable-stage neuroblastoma: a report from the Children's Oncology Group. J Clin Oncol. 2008;26:913-8 pubmed publisher
    b>MYCN amplification is rarely detected in patients with favorable-stage neuroblastoma (NB)...
  47. Suenaga Y, Kaneko Y, Matsumoto D, Hossain M, Ozaki T, Nakagawara A. Positive auto-regulation of MYCN in human neuroblastoma. Biochem Biophys Res Commun. 2009;390:21-6 pubmed publisher
    b>MYCN oncogene is one of the most important regulators affecting the prognosis of neuroblastoma and is frequently amplified in the high-risk subsets...
  48. Gu L, Zhang H, He J, Li J, Huang M, Zhou M. MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells. Oncogene. 2012;31:1342-53 pubmed publisher
    The MYCN gene has a critical role in determining the clinical behavior of neuroblastoma...
  49. Kryh H, Abrahamsson J, Jegerås E, Sjöberg R, Devenney I, Kogner P, et al. MYCN amplicon junctions as tumor-specific targets for minimal residual disease detection in neuroblastoma. Int J Oncol. 2011;39:1063-71 pubmed publisher
    The MYCN gene is frequently amplified in unfavorable neuroblastoma tumors...
  50. Marshall G, Liu P, Gherardi S, Scarlett C, Bedalov A, Xu N, et al. SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability. PLoS Genet. 2011;7:e1002135 pubmed publisher
    ..in pre-cancerous cells, and preventative treatment with the SIRT1 inhibitor Cambinol reduced tumorigenesis in TH-MYCN transgenic mice...
  51. Akter J, Takatori A, Hossain M, Ozaki T, Nakazawa A, Ohira M, et al. Expression of NLRR3 orphan receptor gene is negatively regulated by MYCN and Miz-1, and its downregulation is associated with unfavorable outcome in neuroblastoma. Clin Cancer Res. 2011;17:6681-92 pubmed publisher
    ..NLRR3 and MYCN expressions in NBL cell lines were analyzed after induction of cell differentiation, MYCN knockdown, and ..
  52. Helland A, Anglesio M, George J, Cowin P, Johnstone C, House C, et al. Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers. PLoS ONE. 2011;6:e18064 pubmed publisher
    ..DNA copy number and gene expression of HMGA2, alleles of Let-7, LIN28, LIN28B, MYC, MYCN, DICER1, and RNASEN were measured using microarray and quantitative reverse transcriptase PCR...
  53. Schramm A, Köster J, Marschall T, Martin M, Schwermer M, Fielitz K, et al. Next-generation RNA sequencing reveals differential expression of MYCN target genes and suggests the mTOR pathway as a promising therapy target in MYCN-amplified neuroblastoma. Int J Cancer. 2013;132:E106-15 pubmed publisher
    ..Neuroblastoma is a tumor of early childhood characterized by heterogeneous clinical courses. Amplification of the MYCN oncogene is a marker of poor patient outcome in this disease...
  54. Molenaar J, Domingo Fernández R, Ebus M, Lindner S, Koster J, Drabek K, et al. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet. 2012;44:1199-206 pubmed publisher
    ..LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells...
  55. Valentijn L, Koster J, Haneveld F, Aissa R, van Sluis P, Broekmans M, et al. Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification. Proc Natl Acad Sci U S A. 2012;109:19190-5 pubmed publisher
    Neuroblastoma is a pediatric tumor of the sympathetic nervous system. MYCN (V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived [avian]) is amplified in 20% of neuroblastomas, and these tumors carry a poor prognosis...
  56. De Preter K, Speleman F, Combaret V, Lunec J, Laureys G, Eussen B, et al. Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a real-time quantitative PCR assay. Mod Pathol. 2002;15:159-66 pubmed
    Amplification of the proto-oncogene MYCN is a strong adverse prognostic factor in neuroblastoma patients in all tumor stages...
  57. Jopling C, Willis A. N-myc translation is initiated via an internal ribosome entry segment that displays enhanced activity in neuronal cells. Oncogene. 2001;20:2664-70 pubmed
    ..The discovery of an IRES that displays enhanced activity in neuronal cell lines has important potential as a tool for protein expression in neural tissue. ..
  58. Wei J, Song Y, Durinck S, Chen Q, Cheuk A, Tsang P, et al. The MYCN oncogene is a direct target of miR-34a. Oncogene. 2008;27:5204-13 pubmed publisher
    Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype...
  59. Ciani E, Severi S, Contestabile A, Bartesaghi R, Contestabile A. Nitric oxide negatively regulates proliferation and promotes neuronal differentiation through N-Myc downregulation. J Cell Sci. 2004;117:4727-37 pubmed
  60. Cui H, Li T, Ding H. Linking of N-Myc to death receptor machinery in neuroblastoma cells. J Biol Chem. 2005;280:9474-81 pubmed
    The oncogene MYCN is amplified in aggressive neuroblastomas in which caspase-8, an essential component of death receptor pathways, is frequently inactivated, suggesting a critical role of death receptor-mediated apoptosis in suppression ..
  61. Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, et al. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell. 2009;15:67-78 pubmed publisher
    In human neuroblastoma, amplification of the MYCN gene predicts poor prognosis and resistance to therapy...
  62. Hogarty M, Norris M, Davis K, Liu X, Evageliou N, Hayes C, et al. ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma. Cancer Res. 2008;68:9735-45 pubmed publisher
    Neuroblastoma is a frequently lethal childhood tumor in which MYC gene deregulation, commonly as MYCN amplification, portends poor outcome. Identifying the requisite biopathways downstream of MYC may provide therapeutic opportunities...
  63. Valentijn L, Koppen A, van Asperen R, Root H, Haneveld F, Versteeg R. Inhibition of a new differentiation pathway in neuroblastoma by copy number defects of N-myc, Cdc42, and nm23 genes. Cancer Res. 2005;65:3136-45 pubmed
    ..Three regions of chromosomal gain and loss thus affect genes functioning in one pathway in neuroblastoma. They converge to bring the pathway out of balance and prevent Cdc42 mediated differentiation. ..
  64. Gualdrini F, Corvetta D, Cantilena S, Chayka O, Tanno B, Raschellà G, et al. Addiction of MYCN amplified tumours to B-MYB underscores a reciprocal regulatory loop. Oncotarget. 2010;1:278-88 pubmed
    b>MYCN is a member of the MYC family of oncoproteins frequently amplified or overexpressed in aggressive, paediatric tumours of the nervous system...
  65. Iraci N, Diolaiti D, Papa A, Porro A, Valli E, Gherardi S, et al. A SP1/MIZ1/MYCN repression complex recruits HDAC1 at the TRKA and p75NTR promoters and affects neuroblastoma malignancy by inhibiting the cell response to NGF. Cancer Res. 2011;71:404-12 pubmed publisher
    ..Interestingly, TRKA and p75NTR expression is often attenuated in aggressive MYCN-amplified tumors, suggesting a causal link between elevated MYCN activity and the transcriptional repression of ..
  66. Liu T, Tee A, Porro A, Smith S, Dwarte T, Liu P, et al. Activation of tissue transglutaminase transcription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis. Proc Natl Acad Sci U S A. 2007;104:18682-7 pubmed
    ..Taken together, our data indicate the critical roles of HDAC1 and TG2 in Myc-induced oncogenesis and have significant implications for the use of HDAC inhibitor therapy in Myc-driven oncogenesis. ..
  67. De Brouwer S, De Preter K, Kumps C, Zabrocki P, Porcu M, Westerhout E, et al. Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification. Clin Cancer Res. 2010;16:4353-62 pubmed publisher
    ..7% of the mutated cases, respectively). Interestingly, the F1174 mutations occurred in a high proportion of MYCN-amplified cases (P = 0...
  68. Kang J, Rychahou P, Ishola T, Qiao J, Evers B, Chung D. MYCN silencing induces differentiation and apoptosis in human neuroblastoma cells. Biochem Biophys Res Commun. 2006;351:192-7 pubmed
    b>MYCN amplification strongly correlates with unfavorable outcomes in patients with neuroblastoma. The aim of this study was to investigate the role of MYCN in neuroblastoma cell differentiation and apoptosis...
  69. Swartling F, Grimmer M, Hackett C, Northcott P, Fan Q, Goldenberg D, et al. Pleiotropic role for MYCN in medulloblastoma. Genes Dev. 2010;24:1059-72 pubmed publisher
    ..To identify common signaling abnormalities, we profiled mRNA, demonstrating misexpression of MYCN in the majority of human MB and negligible expression in normal cerebella...
  70. Jeison M, Ash S, Halevy Berko G, Mardoukh J, Luria D, Avigad S, et al. 2p24 Gain region harboring MYCN gene compared with MYCN amplified and nonamplified neuroblastoma: biological and clinical characteristics. Am J Pathol. 2010;176:2616-25 pubmed publisher
    Although the role of MYCN amplification in neuroblastoma is well established, the biological and clinical characteristics of the 2p gain region harboring the MYCN gene remain unclear...
  71. Slack A, Chen Z, Tonelli R, Pule M, Hunt L, Pession A, et al. The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma. Proc Natl Acad Sci U S A. 2005;102:731-6 pubmed
    The MYCN oncogene is the major negative prognostic marker in neuroblastoma with important roles in both the pathogenesis and clinical behavior of this aggressive malignancy...
  72. Murphy D, Buckley P, Bryan K, Das S, Alcock L, Foley N, et al. Global MYCN transcription factor binding analysis in neuroblastoma reveals association with distinct E-box motifs and regions of DNA hypermethylation. PLoS ONE. 2009;4:e8154 pubmed publisher
    ..The single most important prognostic indicator of poor clinical outcome in this disease is genomic amplification of MYCN, a member of a family of oncogenic transcription factors...
  73. Petroni M, Veschi V, Prodosmo A, Rinaldo C, Massimi I, Carbonari M, et al. MYCN sensitizes human neuroblastoma to apoptosis by HIPK2 activation through a DNA damage response. Mol Cancer Res. 2011;9:67-77 pubmed publisher
    b>MYCN amplification occurs in approximately 20% of human neuroblastomas and is associated with early tumor progression and poor outcome, despite intensive multimodal treatment...
  74. Koppen A, Ait Aissa R, Hopman S, Koster J, Haneveld F, Versteeg R, et al. Dickkopf-1 is down-regulated by MYCN and inhibits neuroblastoma cell proliferation. Cancer Lett. 2007;256:218-28 pubmed
    ..Twenty percent of neuroblastomas show amplification of the MYCN oncogene, which correlates with poor prognosis...
  75. Jacobs J, van Bokhoven H, van Leeuwen F, Hulsbergen van de Kaa C, de Vries I, Adema G, et al. Regulation of MYCN expression in human neuroblastoma cells. BMC Cancer. 2009;9:239 pubmed publisher
    Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN-amplification does not automatically result in higher expression of MYCN in children with NB...
  76. Ochiai H, Takenobu H, Nakagawa A, Yamaguchi Y, Kimura M, Ohira M, et al. Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma. Oncogene. 2010;29:2681-90 pubmed publisher
    ..In this paper, we clarified the direct binding of MYCN to Bmi1 promoter and upregulation of Bmi1 transcription by MYCN...
  77. Beierle E, Trujillo A, Nagaram A, Kurenova E, Finch R, Ma X, et al. N-MYC regulates focal adhesion kinase expression in human neuroblastoma. J Biol Chem. 2007;282:12503-16 pubmed
    ..The results indicate that N-MYC regulation of FAK expression can control cellular functions in isogenic N-MYC(-/+) (Tet(+/-)) neuroblastoma cell lines. ..