Expression of Mutant p53 Proteins Implicates a Lineage Relationship between Neural Stem Cells and Malignant Astrocytic Glioma in a Murine Model

Recent studies have identified genes and core pathways that are altered in human glioblastoma. However, the mechanisms by which alterations of these glioblastoma genes singly and cooperatively transform brain cells remain poorly understood. Further, the cell of origin of glioblastoma is largely elus...

Full description

Saved in:
Bibliographic Details
Published inCancer cell Vol. 15; no. 6; pp. 514 - 526
Main Authors Wang, Yuan, Yang, Jiong, Zheng, Huarui, Tomasek, Gerald J., Zhang, Peng, McKeever, Paul E., Lee, Eva Y.-H.P., Zhu, Yuan
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 02.06.2009
Subjects
Animals
Astrocytes - pathology
Astrocytes - physiology
Astrocytoma - metabolism
Astrocytoma - pathology
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Cell Differentiation
Cell Lineage - physiology
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
CELLCYCLE
Corpus Callosum - metabolism
Corpus Callosum - pathology
Disease Models, Animal
Mice
Mice, Knockout
Multipotent Stem Cells - pathology
Multipotent Stem Cells - physiology
Mutation
Neurons - pathology
Neurons - physiology
Signal Transduction - physiology
STEMCELL
Tumor Suppressor Protein p53 - biosynthesis
Tumor Suppressor Protein p53 - genetics
STEMCELL
CELLCYCLE
Online AccessGet full text

Cover

More Information
Summary:Recent studies have identified genes and core pathways that are altered in human glioblastoma. However, the mechanisms by which alterations of these glioblastoma genes singly and cooperatively transform brain cells remain poorly understood. Further, the cell of origin of glioblastoma is largely elusive. By targeting a p53 in-frame deletion mutation to the brain, we show that p53 deficiency provides no significant growth advantage to adult brain cells, but appears to induce pleiotropic accumulation of cooperative oncogenic alterations driving gliomagenesis. Our data show that accumulation of a detectable level of mutant p53 proteins occurs first in neural stem cells in the subventricular zone (SVZ) and that subsequent expansion of mutant p53-expressing Olig2 + transit-amplifying progenitor-like cells in the SVZ-associated areas initiates glioma formation.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors contributed equally to this work
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2009.04.001