Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2009-7-16
pubmed:abstractText
Glioblastoma multiforme (GBM) is one of the most common and aggressive types of brain tumors. In GBM, a subpopulation of CD133-positive cancer initiating cells displays stem cell characteristics. The Polycomb group (PcG) and oncogene BMI1 is part of the Polycomb repressive complex 1 (PRC1) that regulates gene expression by modifying chromatin organization. Here we show that BMI1 is expressed in human GBM tumors and highly enriched in CD133-positive cells. Stable BMI1 knockdown using short hairpin RNA-expressing lentiviruses resulted in inhibition of clonogenic potential in vitro and of brain tumor formation in vivo. Cell biology studies support the notion that BMI1 prevents CD133-positive cell apoptosis and/or differentiation into neurons and astrocytes, depending on the cellular context. Gene expression analyses suggest that BMI1 represses alternate tumor suppressor pathways that attempt to compensate for INK4A/ARF/P53 deletion and PI(3)K/AKT hyperactivity. Inhibition of EZH2, the main component of the PRC2, also impaired GBM tumor growth. Our results reveal that PcG proteins are involved in GBM tumor growth and required to sustain cancer initiating stem cell renewal.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AC133 antigen, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD, http://linkedlifedata.com/resource/pubmed/chemical/BMI1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/EZH2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8884-96
pubmed:meshHeading
pubmed-meshheading:19605626-Analysis of Variance, pubmed-meshheading:19605626-Animals, pubmed-meshheading:19605626-Antigens, CD, pubmed-meshheading:19605626-Apoptosis, pubmed-meshheading:19605626-Brain Neoplasms, pubmed-meshheading:19605626-Cell Differentiation, pubmed-meshheading:19605626-Cell Line, Tumor, pubmed-meshheading:19605626-Cell Transdifferentiation, pubmed-meshheading:19605626-Cell Transformation, Neoplastic, pubmed-meshheading:19605626-Cells, Cultured, pubmed-meshheading:19605626-Chromatin Immunoprecipitation, pubmed-meshheading:19605626-DNA-Binding Proteins, pubmed-meshheading:19605626-Disease Models, Animal, pubmed-meshheading:19605626-Flow Cytometry, pubmed-meshheading:19605626-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19605626-Gene Silencing, pubmed-meshheading:19605626-Glioblastoma, pubmed-meshheading:19605626-Glycoproteins, pubmed-meshheading:19605626-Humans, pubmed-meshheading:19605626-Mice, pubmed-meshheading:19605626-Mice, Inbred NOD, pubmed-meshheading:19605626-Mice, SCID, pubmed-meshheading:19605626-Neoplastic Stem Cells, pubmed-meshheading:19605626-Nuclear Proteins, pubmed-meshheading:19605626-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19605626-Peptides, pubmed-meshheading:19605626-Proto-Oncogene Proteins, pubmed-meshheading:19605626-RNA, Small Interfering, pubmed-meshheading:19605626-Repressor Proteins, pubmed-meshheading:19605626-Transcription Factors, pubmed-meshheading:19605626-Tumor Stem Cell Assay
pubmed:year
2009
pubmed:articleTitle
BMI1 sustains human glioblastoma multiforme stem cell renewal.
pubmed:affiliation
Developmental Biology Laboratory, Maisonneuve-Rosemont Hospital, Montréal, Québec H1T 2M4, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't