MYCN oncoprotein targets and their therapeutic potential

被引:90
作者
Bell, Emma [1 ]
Chen, Lindi [1 ]
Liu, Tao [2 ]
Marshall, Glenn M. [2 ]
Lunec, John [1 ]
Tweddle, Deborah A. [1 ]
机构
[1] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Childrens Canc Inst Australia, Sydney, NSW, Australia
基金
英国医学研究理事会;
关键词
MYCN; Microarrays; Neuroblastoma; Target genes; HUMAN NEUROBLASTOMA-CELLS; DIRECT TRANSCRIPTIONAL TARGET; DEACETYLASE INHIBITOR BL1521; PEPTIDE NUCLEIC-ACID; ARF TUMOR-SUPPRESSOR; MRP GENE-EXPRESSION; N-MYC; C-MYC; ORNITHINE-DECARBOXYLASE; CENTROSOME AMPLIFICATION;
D O I
10.1016/j.canlet.2010.01.015
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The MYCN oncogene encodes a transcription factor which is amplified in up to 40% of high risk neuroblastomas. MYCN amplification is a well-established poor prognostic marker in neuroblastoma, however the role of MYCN expression and the mechanisms by which it acts to promote an aggressive phenotype remain largely unknown. This review discusses the current evidence identifying the direct and indirect downstream transcriptional targets of MYCN from recent studies, with particular reference to how MYCN affects the cell cycle, DNA damage response, differentiation and apoptosis in neuroblastoma. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:144 / 157
页数:14
相关论文
共 154 条
  • [61] ODC1 Is a Critical Determinant of MYCN Oncogenesis and a Therapeutic Target in Neuroblastoma
    Hogarty, Michael D.
    Norris, Murray D.
    Davis, Kimberly
    Liu, Xueyuan
    Evageliou, Nicholas F.
    Hayes, Candace S.
    Pawel, Bruce
    Guo, Rong
    Zhao, Huaqing
    Sekyere, Eric
    Keating, Joanna
    Thomas, Wayne
    Cheng, Ngan Ching
    Murray, Jayne
    Smith, Janice
    Sutton, Rosemary
    Venn, Nicola
    London, Wendy B.
    Buxton, Allen
    Gilmour, Susan K.
    Marshall, Glenn M.
    Haber, Michelle
    [J]. CANCER RESEARCH, 2008, 68 (23) : 9735 - 9745
  • [62] N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1(NLRR1) gene in neuroblastoma
    Hossain, M. S.
    Ozaki, T.
    Wang, H.
    Nakagawa, A.
    Takenobu, H.
    Ohira, M.
    Kamijo, T.
    Nakagawara, A.
    [J]. ONCOGENE, 2008, 27 (46) : 6075 - 6082
  • [63] Dickkopf-3/REIC functions as a suppressor gene of tumor growth
    Hsieh, SY
    Hsieh, PS
    Chiu, CT
    Chen, WY
    [J]. ONCOGENE, 2004, 23 (57) : 9183 - 9189
  • [64] Expression profiling reveals off-target gene regulation by RNAi
    Jackson, AL
    Bartz, SR
    Schelter, J
    Kobayashi, SV
    Burchard, J
    Mao, M
    Li, B
    Cavet, G
    Linsley, PS
    [J]. NATURE BIOTECHNOLOGY, 2003, 21 (06) : 635 - 637
  • [65] An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant
    Ji, P
    Jiang, H
    Rekhtman, K
    Bloom, J
    Ichetovkin, M
    Pagano, M
    Zhu, L
    [J]. MOLECULAR CELL, 2004, 16 (01) : 47 - 58
  • [66] Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo
    Johnsen, J. I.
    Segerstrom, L.
    Orrego, A.
    Elfman, L.
    Henriksson, M.
    Kagedal, B.
    Eksborg, S.
    Sveinbjornsson, B.
    Kogner, P.
    [J]. ONCOGENE, 2008, 27 (20) : 2910 - 2922
  • [67] The concept of synthetic lethality in the context of anticancer therapy
    Kaelin, WG
    [J]. NATURE REVIEWS CANCER, 2005, 5 (09) : 689 - 698
  • [68] N-myc is a novel regulator of PI3K-mediated VEGF expression in neuroblastoma
    Kang, J.
    Rychahou, P. G.
    Ishola, T. A.
    Mourot, J. M.
    Evers, B. M.
    Chung, D. H.
    [J]. ONCOGENE, 2008, 27 (28) : 3999 - 4007
  • [69] MYCN silencing induces differentiation and apoptosis in human neuroblastoma cells
    Kang, Jung-Hee
    Rychahou, Piotr G.
    Ishola, Titilope A.
    Qiao, Jingbo
    Evers, B. Mark
    Chung, Dal H.
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 351 (01) : 192 - 197
  • [70] Regulation of prostate cell growth and morphogenesis by Dickkopf-3
    Kawano, Y.
    Kitaoka, M.
    Hamada, Y.
    Walker, M. M.
    Waxman, J.
    Kypta, R. M.
    [J]. ONCOGENE, 2006, 25 (49) : 6528 - 6537