Authors: | Barrett, L. E.; Granot, Z.; Coker, C.; Iavarone, A.; Hambardzumyan, D.; Holland, E. C.; Nam, H. S.; Benezra, R. |
Article Title: | Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma |
Abstract: | Within high-grade gliomas, the precise identities and functional roles of stem-like cells remain unclear. In the normal neurogenic niche, ID (Inhibitor of DNA-binding) genes maintain self-renewal and multipotency of adult neural stem cells. Using PDGF- and KRAS-driven murine models of gliomagenesis, we show that high Id1 expression (Id1 high) identifies tumor cells with high self-renewal capacity, while low Id1 expression (Id1 low) identifies tumor cells with proliferative potential but limited self-renewal capacity. Surprisingly, Id1 low cells generate tumors more rapidly and with higher penetrance than Id1 high cells. Further, eliminating tumor cell self-renewal through deletion of Id1 has modest effects on animal survival, while knockdown of Olig2 within Id1 low cells has a significant survival benefit, underscoring the importance of non-self-renewing lineages in disease progression. © 2012 Elsevier Inc. |
Keywords: | platelet derived growth factor; cancer survival; controlled study; protein expression; gene deletion; nonhuman; glioma; cancer grading; cell proliferation; animal cell; mouse; inhibitor of differentiation 1; oligodendrocyte transcription factor 2; animal experiment; animal model; cell renewal; carcinogenesis; cell lineage; tumor cell; gene silencing; tumor growth; k ras protein; penetrance; cell self renewal |
Journal Title: | Cancer Cell |
Volume: | 21 |
Issue: | 1 |
ISSN: | 1535-6108 |
Publisher: | Cell Press |
Date Published: | 2012-01-17 |
Start Page: | 11 |
End Page: | 24 |
Language: | English |
DOI: | 10.1016/j.ccr.2011.11.025 |
PROVIDER: | scopus |
PUBMED: | 22264785 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 1 March 2012" - "CODEN: CCAEC" - "Source: Scopus" |