| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology and Genetics |
Departments of Pediatrics [J. M. S., S. E. P., M. K. B.], Pathology [M. J. H.], Molecular and Human Genetics [S-Y. C.], and The DeBakey Department of Surgery [S. M. B., J. G. N.], Baylor College of Medicine, Houston, Texas 77030; The Center for Cell and Gene Therapy, Houston, Texas 77030 [J. M. S., S-Y. C., M. K. B., J. G. N.]; Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, Texas 77030 [S. S.]; and Incyte Genomics, Palo Alto, California 94304 [S. S.]
The MYCN oncogene is amplified in 
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. Microarray analysis of RNA from neuroblastoma primary cell cultures revealed 10-fold higher MCM7 expression in MYCN-amplified versus nonamplified tumors. MCM7 is an essential component of DNA replication licensing factor, a hexameric protein complex that regulates DNA synthesis during the cell cycle, preventing rereplication and ensuring maintenance of DNA euploidy. Additional experiments demonstrated markedly increased expression of MCM7 RNA and protein in MYCN-amplified neuroblastoma tumors and cell lines. Induction of MYCN in conditional cell lines results in increased expression of endogenous MCM7 mRNA and a 3-fold increase in protein levels. In addition, luciferase activity from MCM7 promoter/luciferase gene reporter constructs was significantly increased under MYCN-induced conditions. Specific electrophoretic mobility shifts of MCM7 promoter sequences are detected in extracts of MYCN-amplified cells. These findings demonstrate that in neuroblastoma, the MYCN oncogene directly activates genes required for DNA replication, and this may contribute to neoplastic transformation of these MYCN-amplified tumors.
This article has been cited by other articles:
|
|
 |
|
  L. Chesler, C. Schlieve, D. D. Goldenberg, A. Kenney, G. Kim, A. McMillan, K. K. Matthay, D. Rowitch, and W. A. Weiss Inhibition of Phosphatidylinositol 3-Kinase Destabilizes Mycn Protein and Blocks Malignant Progression in Neuroblastoma Cancer Res., August 15, 2006; 66(16): 8139 - 8146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, S. Diskin, E. Rappaport, E. Attiyeh, Y. Mosse, D. Shue, E. Seiser, J. Jagannathan, S. Shusterman, M. Bansal, et al. Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number. Cancer Res., June 15, 2006; 66(12): 6050 - 6062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Giannini, F. Cerignoli, M. Mellone, I. Massimi, C. Ambrosi, C. Rinaldi, C. Dominici, L. Frati, I. Screpanti, and A. Gulino High Mobility Group A1 Is a Molecular Target for MYCN in Human Neuroblastoma Cancer Res., September 15, 2005; 65(18): 8308 - 8316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aoyama, T. Ozaki, H. Inuzuka, D. Tomotsune, J. Hirato, Y. Okamoto, H. Tokita, M. Ohira, and A. Nakagawara LMO3 Interacts with Neuronal Transcription Factor, HEN2, and Acts as an Oncogene in Neuroblastoma Cancer Res., June 1, 2005; 65(11): 4587 - 4597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Tsvetkov and D. F. Stern Interaction of Chromatin-associated Plk1 and Mcm7 J. Biol. Chem., March 25, 2005; 280(12): 11943 - 11947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Thomas, C. A. Messam, B. A. Spengler, J. L. Biedler, and R. A. Ross Nestin Is a Potential Mediator of Malignancy in Human Neuroblastoma Cells J. Biol. Chem., July 2, 2004; 279(27): 27994 - 27999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Forsburg Eukaryotic MCM Proteins: Beyond Replication Initiation Microbiol. Mol. Biol. Rev., March 1, 2004; 68(1): 109 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alaminos, J. Mora, N.-K. V. Cheung, A. Smith, J. Qin, L. Chen, and W. L. Gerald Genome-wide Analysis of Gene Expression Associated with MYCN in Human Neuroblastoma Cancer Res., August 1, 2003; 63(15): 4538 - 4546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. G. Oliver, L. L. Grasfeder, A. L. Carroll, C. Kaiser, C. L. Gillingham, S. M. Lin, R. Wickramasinghe, M. P. Scott, and R. J. Wechsler-Reya Transcriptional profiling of the Sonic hedgehog response: A critical role for N-myc in proliferation of neuronal precursors PNAS, June 10, 2003; 100(12): 7331 - 7336. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
