PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry.
Previous studies have demonstrated that a small subpopulation of brain tumor cells share key characteristics with neural stem/progenitor cells in terms of phenotype and behavior. These findings suggest that brain tumors might contain "cancer stem cells" that are critical for tumor growth. However, the molecular pathways governing such stem cell-like behavior remain largely elusive. Our previous study suggests that the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene, one of the most frequently mutated genes in glioblastomas, restricts neural stem/progenitor cell proliferation in vivo. In the present study, we sought to determine the role of PTEN in long-term maintenance of stem cell-like properties, cell cycle entry and progression, and growth factor dependence and gene expression. Our results demonstrate an enhanced self-renewal capacity and G(0)-G(1) cell cycle entry and decreased growth factor dependency of Pten null neural/stem progenitor cells. Therefore, loss of PTEN leads to cell physiological changes, which collectively are sufficient to increase the pool of self-renewing neural stem cells and promote their escape from the homeostatic mechanisms of proliferation control.
Groszer
Matthias
M
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Erickson
Rebecca
R
Scripture-Adams
Deirdre D
DD
Dougherty
Joseph D
JD
Le Belle
Janel
J
Zack
Jerome A
JA
Geschwind
Daniel H
DH
Liu
Xin
X
Kornblum
Harley I
HI
Wu
Hong
H
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D017353:Gene Deletion; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
D016222:Fibroblast Growth Factor 2; D051059:PTEN Phosphohydrolase