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

Matthias Groszer, Rebecca Erickson, Deirdre D. Scripture-Adams, Joseph D. Dougherty, Janel Le Belle, Jerome A. Zack, Daniel H. Geschwind, Xin Liu, Harley I. Kornblum, Hong Wu

Research output: Contribution to journalArticle

234 Scopus citations

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 longterm 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-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.

Original languageEnglish
Pages (from-to)111-116
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number1
DOIs
StatePublished - Jan 3 2006
Externally publishedYes

Keywords

  • Brain tumor
  • Conditional knockout mouse model
  • Growth factor dependency
  • Tumor suppressor

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    Groszer, M., Erickson, R., Scripture-Adams, D. D., Dougherty, J. D., Le Belle, J., Zack, J. A., Geschwind, D. H., Liu, X., Kornblum, H. I., & Wu, H. (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), 111-116. https://doi.org/10.1073/pnas.0509939103