PMID- 20190806
OWN - NLM
STAT- MEDLINE
DCOM- 20100514
LR  - 20211203
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 29
IP  - 18
DP  - 2010 May 6
TI  - Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of 
      KIF1Bbeta and TSLC1 in neuroblastoma.
PG  - 2681-90
LID - 10.1038/onc.2010.22 [doi]
AB  - Recent advances in neuroblastoma (NB) research addressed that epigenetic 
      alterations such as hypermethylation of promoter sequences, with consequent 
      silencing of tumor-suppressor genes, can have significant roles in the 
      tumorigenesis of NB. However, the exact role of epigenetic alterations, except 
      for DNA hypermethylation, remains to be elucidated in NB research. In this paper, 
      we clarified the direct binding of MYCN to Bmi1 promoter and upregulation of Bmi1 
      transcription by MYCN. Mutation introduction into an MYCN binding site in the 
      Bmi1 promoter suggests that MYCN has more important roles in the transcription of 
      Bmi1 than E2F-related Bmi1 regulation. A correlation between MYCN and polycomb 
      protein Bmi1 expression was observed in primary NB tumors. Expression of Bmi1 
      resulted in the acceleration of proliferation and colony formation in NB cells. 
      Bmi1-related inhibition of NB cell differentiation was confirmed by neurite 
      extension assay and analysis of differentiation marker molecules. Intriguingly, 
      the above-mentioned Bmi1-related regulation of the NB cell phenotype seems not to 
      be mediated only by p14ARF/p16INK4a in NB cells. Expression profiling analysis 
      using a tumor-specific cDNA microarray addressed the Bmi1-dependent repression of 
      KIF1Bbeta and TSLC1, which have important roles in predicting the prognosis of 
      NB. Chromatin immunoprecipitation assay showed that KIF1Bbeta and TSLC1 are 
      direct targets of Bmi1 in NB cells. These findings suggest that MYCN induces Bmi1 
      expression, resulting in the repression of tumor suppressors through Polycomb 
      group gene-mediated epigenetic chromosome modification. NB cell proliferation and 
      differentiation seem to be partially dependent on the MYCN/Bmi1/tumor-suppressor 
      pathways.
FAU - Ochiai, H
AU  - Ochiai H
AD  - Division of Biochemistry and Molecular Carcinogenesis, Chiba Cancer Center 
      Research Institute, Chiba, Japan.
FAU - Takenobu, H
AU  - Takenobu H
FAU - Nakagawa, A
AU  - Nakagawa A
FAU - Yamaguchi, Y
AU  - Yamaguchi Y
FAU - Kimura, M
AU  - Kimura M
FAU - Ohira, M
AU  - Ohira M
FAU - Okimoto, Y
AU  - Okimoto Y
FAU - Fujimura, Y
AU  - Fujimura Y
FAU - Koseki, H
AU  - Koseki H
FAU - Kohno, Y
AU  - Kohno Y
FAU - Nakagawara, A
AU  - Nakagawara A
FAU - Kamijo, T
AU  - Kamijo T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100301
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (BMI1 protein, human)
RN  - 0 (CADM1 protein, human)
RN  - 0 (Cell Adhesion Molecule-1)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Immunoglobulins)
RN  - 0 (KIF1B protein, human)
RN  - 0 (MYCN protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (N-Myc Proto-Oncogene Protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
CIN - Epigenomics. 2010 Oct;2(5):610. PMID: 22232788
MH  - Cell Adhesion Molecule-1
MH  - Cell Adhesion Molecules
MH  - Cell Differentiation
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - Immunoglobulins/*genetics
MH  - Kinesins/*genetics
MH  - Membrane Proteins/*genetics
MH  - N-Myc Proto-Oncogene Protein
MH  - Neuroblastoma/*etiology/pathology
MH  - Nuclear Proteins/*genetics/*physiology
MH  - Oncogene Proteins/*physiology
MH  - Polycomb Repressive Complex 1
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*genetics
MH  - Repressor Proteins/*genetics
MH  - Transcription, Genetic
MH  - Tumor Suppressor Proteins/*genetics
EDAT- 2010/03/02 06:00
MHDA- 2010/05/15 06:00
CRDT- 2010/03/02 06:00
PHST- 2010/03/02 06:00 [entrez]
PHST- 2010/03/02 06:00 [pubmed]
PHST- 2010/05/15 06:00 [medline]
AID - onc201022 [pii]
AID - 10.1038/onc.2010.22 [doi]
PST - ppublish
SO  - Oncogene. 2010 May 6;29(18):2681-90. doi: 10.1038/onc.2010.22. Epub 2010 Mar 1.