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PMID: 17217625 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Notch signaling enhances nestin expression in gliomas.

Neoplasia (New York, N.Y.) ·Vol. 8 ·No. 12 ·2006-12-00 ·Pages 1072-82

Shih AH, Holland EC

Abstract

Recent findings suggest that Notch signaling is active in brain tumors and stem cells, and that stem cells or cells with progenitor characteristics contribute to brain tumor formation. These stem cells are marked by expression of several markers, including nestin, an intermediate filament protein. We have studied how the Notch signaling pathway affects nestin expression in brain tumors. We find that Notch receptors and ligands are expressed in vitro and in human samples of glioblastomas, the highest grade of malignant gliomas. In culture, Notch activity activates the nestin promoter. Activation of the Notch pathway also occurs in a glioblastoma multiforme mouse model induced by Kras, with translational regulation playing a role in Notch expression. Combined activation of Notch and Kras in wild-type nestin-expressing cells leads to their expansion within the subventricular zone and retention of proliferation and nestin expression. However, activation of Notch alone is unable to induce this cellular expansion. These data suggest that Notch may have a contributing role in the stem-like character of glioma cells.

MeSH Terms
Animals Base Sequence Brain Neoplasms/genetics,metabolism,pathology Chickens Gene Expression Regulation, Neoplastic Glioblastoma/genetics,metabolism,pathology Glioma/genetics,metabolism,pathology Humans Intermediate Filament Proteins/biosynthesis,genetics Mice Mice, Transgenic Molecular Sequence Data Nerve Tissue Proteins/biosynthesis,genetics Nestin Rats Receptors, Notch/genetics,physiology Signal Transduction/genetics,physiology Stem Cells/metabolism,pathology Up-Regulation/physiology
Chemicals
Intermediate Filament Proteins NES protein, human Nerve Tissue Proteins Nes protein, mouse Nes protein, rat Nestin Receptors, Notch
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Shih Alan H
Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Holland Eric C
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1476-5586
DOI
10.1593/neo.06526
Published
2006-12-00
Pages
1072-82
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1790729
Subset
IM
Grants
NCI NIH HHS · R01 CA099489 · United States
NIGMS NIH HHS · T32 GM007739 · United States
NIGMS NIH HHS · GM07739 · United States
NCI NIH HHS · UO1CA894314-1 · United States
External Links
PubMed source DOI: 10.1593/neo.06526 PMC Full Text View journal details
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