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

Groszer, Matthias and Erickson, Rebecca and Scripture-Adams, Dierdre D. and Dougherty, Jospeh D. and Le Belle, Janel and Zack, Jerome A. and Geschwind, Daniel H. and Liu, Xin and Kornblum, Harley I. and Wu, Hong (2006) 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, 103 (1). pp. 111-116. ISSN 0027-8424. PMCID PMC1325011. https://resolver.caltech.edu/CaltechAUTHORS:GROpnas06

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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 G0-G1 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.0509939103DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc1325011/PubMed CentralArticle
ORCID:
AuthorORCID
Geschwind, Daniel H.0000-0003-2896-3450
Additional Information:© 2006 by The National Academy of Sciences of the USA Communicated by Michael E. Phelps, University of California School of Medicine, Los Angeles, CA, November 16, 2005 (received for review October 3, 2005). Published online before print December 22, 2005, 10.1073/pnas.0509939103 We thank Dr. Paul Mischel and members of our laboratories for helpful comments and suggestions. M.G. was partially supported by the Swiss National Science Foundation. J.D.D. was supported by a Howard Hughes Medical Institute Predoctoral Fellowship. D.D.S.-A. was supported by an Amgen/Esther Hayes AIDS Institute Graduate Fellowship. This work was supported by grants from Henry Singleton Brain Research Program (to H.W. and H.I.K.) and The James S. MacDonnell Foundation (to H.W.); by National Institutes of Health Grant NS38439 and The Brain Tumor Society (to X.L.); and by National Institute of Mental Health Grant 65756 and the Jonsson Comprehensive Cancer Center (to H.I.K.). Author contributions: M.G., R.E., D.D.S.-A., J.A.Z., D.H.G., X.L., H.I.K., and H.W. designed research; M.G., R.E., D.D.S.-A., J.D.D., and J.L.B. performed research; M.G., R.E., D.D.S.-A., J.D.D., J.L.B., J.A.Z., D.H.G., X.L., H.I.K., and H.W. analyzed data; and M.G., R.E., D.D.S.-A., J.D.D., J.L.B., J.A.Z., D.H.G., X.L., H.I.K., and H.W. wrote the paper. Conflict of interest statement: No conflicts declared.
Funders:
Funding AgencyGrant Number
Swiss National Science Foundation (SNSF)UNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Amgen/Esther Hayes AIDS InstituteUNSPECIFIED
James S. McDonnell FoundationUNSPECIFIED
NIHNS38439
Brain Tumor SocietyUNSPECIFIED
National Institute of Mental Health (NIMH)MH65756
Jonsson Comprehensive Cancer CenterUNSPECIFIED
Subject Keywords:tumor suppressor; conditional knockout mouse model; growth factor dependency; brain tumor
Issue or Number:1
PubMed Central ID:PMC1325011
Record Number:CaltechAUTHORS:GROpnas06
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:GROpnas06
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5971
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:10 Nov 2006
Last Modified:03 Jun 2020 19:25

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