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PMID: 16373498 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 1 ·2006-01-03 ·Pages 111-6

Groszer M, Erickson R, Scripture-Adams DD, Dougherty JD, Le Belle J, Zack JA, Geschwind DH, Liu X, Kornblum HI, Wu H

Abstract

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.

MeSH Terms
Animals Cell Cycle/physiology Cell Differentiation/physiology Cell Proliferation Cerebral Cortex/cytology Fibroblast Growth Factor 2/metabolism Gene Deletion Mice Oligonucleotide Array Sequence Analysis PTEN Phosphohydrolase/genetics,metabolism Stem Cells/cytology,metabolism
Chemicals
Fibroblast Growth Factor 2 PTEN Phosphohydrolase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Groszer Matthias
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Erickson Rebecca
Scripture-Adams Deirdre D
Dougherty Joseph D
Le Belle Janel
Zack Jerome A
Geschwind Daniel H
Liu Xin
Kornblum Harley I
Wu Hong
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0509939103
Published
2006-01-03
Epub
2005-00-22
Pages
111-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1325011
Subset
IM
Grants
PHS HHS · 65756 · United States
NINDS NIH HHS · NS38439 · United States
External Links
PubMed source DOI: 10.1073/pnas.0509939103 PMC Full Text View journal details
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