Published online 31 March 2006
Article |
BMI1 is a target gene of E2F-1 and is strongly expressed in primary neuroblastomas
Institute of Molecular Biology and Tumor Research (IMT) Emil-Mannkopff-Strasse 2, 35033 Marburg, Germany 1 Children's Hospital Deutschhausstrasse 12, 35037 Marburg, Germany
*To whom correspondence should be addressed. Tel: +49 6421 2865390; Fax: +49 6421 2865196; Email: lutz{at}imt.uni-marburg.de
Received January 18, 2006. Revised February 19, 2006. Accepted March 13, 2006.
The oncogene BMI1 encodes a polycomb group transcription factor that is required for embryonic development and self-renewal of stem cells. Despite these important functions little is known about the regulation of BMI1 expression. A cDNA microarray based search for target genes of E2F-1 in neuroblastoma cells expressing a 4-OHT-regulated E2F-1-ER fusion protein identified many hitherto unknown E2F-1 regulated genes. A total of 10% of these genes, including BMI1, encode proteins that function primarily in the regulation of gene expression. The BMI1 promoter contains a putative E2F binding site that was required for the activation of a BMI1 promoter-dependent reporter construct by E2F-1. Chromatin immunoprecipitation revealed 4-OHT-dependent binding of E2F-1-ER and binding of endogenous E2F-1 to the BMI1 promoter in tumor cells. We have previously shown activation of the oncogene MYCN by E2F. Thus, in neuroblastomas deregulated E2F-1 can activate two oncogenes, MYCN and BMI1 that are known to co-operate in tumor formation. Consistent with a role of Bmi1 in neuroblastoma tumorigenesis we found strong Bmi1 expression in primary neuroblastomas. Our results reveal a novel link between E2F and polycomb transcription factors and suggest a role of Bmi1 in neuroblastomas.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Kim and J. Shohet Targeted Molecular Therapy for Neuroblastoma: The ARF/MDM2/p53 Axis J Natl Cancer Inst, November 18, 2009; 101(22): 1527 - 1529. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Colecchia, D. Kottwitz, M. Wagner, C. V. Pfenninger, G. Thiel, I. Tamm, C. Peterson, and U. A. Nuber Tissue-specific regulatory network extractor (TS-REX): a database and software resource for the tissue and cell type-specific investigation of transcription factor-gene networks Nucleic Acids Res., June 1, 2009; 37(11): e82 - e82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Dey, L. Stalker, A. Schnerch, M. Bhatia, J. Taylor-Papidimitriou, and C. Wynder The Histone Demethylase KDM5b/JARID1b Plays a Role in Cell Fate Decisions by Blocking Terminal Differentiation Mol. Cell. Biol., September 1, 2008; 28(17): 5312 - 5327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Douglas, J. H.-R. Hsu, L. Hung, A. Cooper, D. Abdueva, J. van Doorninck, G. Peng, H. Shimada, T. J. Triche, and E. R. Lawlor BMI-1 Promotes Ewing Sarcoma Tumorigenicity Independent of CDKN2A Repression Cancer Res., August 15, 2008; 68(16): 6507 - 6515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Chapman, G. Kelly, and M. A. Knowles Genes Involved in Differentiation, Stem Cell Renewal, and Tumorigenesis Are Modulated in Telomerase-Immortalized Human Urothelial Cells Mol. Cancer Res., July 1, 2008; 6(7): 1154 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mohty, A. S. M. Yong, R. M. Szydlo, J. F. Apperley, and J. V. Melo The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia Blood, July 1, 2007; 110(1): 380 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zanardi, L. Giorgetti, O. A. Botrugno, S. Minucci, P. Milani, P. G. Pelicci, and R. Carbone Immunocell-array for Molecular Dissection of Multiple Signaling Pathways in Mammalian Cells Mol. Cell. Proteomics, May 1, 2007; 6(5): 939 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cui, B. Hu, T. Li, J. Ma, G. Alam, W. T. Gunning, and H.-F. Ding Bmi-1 Is Essential for the Tumorigenicity of Neuroblastoma Cells Am. J. Pathol., April 1, 2007; 170(4): 1370 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-J. Guo, S. Datta, V. Band, and G. P. Dimri Mel-18, a Polycomb Group Protein, Regulates Cell Proliferation and Senescence via Transcriptional Repression of Bmi-1 and c-Myc Oncoproteins Mol. Biol. Cell, February 1, 2007; 18(2): 536 - 546. [Abstract] [Full Text] [PDF]
|
|