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Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

Cited 84 time in Web of Science Cited 88 time in Scopus
Authors
Jeon, Hye-Min; Jin, Xun; Lee, Joong-Seob; Oh, Se-Yeong; Sohn, Young-Woo; Park, Hyo-Jung; Joo, Kyeung Min; Park, Woong-Yang; Nam, Do-Hyun; DePinho, Ronald A; Chin, Lynda; Kim, Hyunggee
Issue Date
2008-08-05
Publisher
Cold Spring Harbor Laboratory Press
Citation
Genes Dev. 22(15): 2028-2033
Keywords
AnimalsAstrocytes/cytology/*physiologyCalcium-Binding Proteins/metabolismCell Culture TechniquesCell Line, Tumor*Cell Transformation, NeoplasticCells, CulturedCerebral Cortex/cytologyCyclin E/*metabolismGlioblastoma/pathologyHumansInhibitor of Differentiation Proteins/*metabolismIntercellular Signaling Peptides and Proteins/metabolismMembrane Proteins/metabolismMiceMice, KnockoutRNA, Messenger/metabolismReceptor, Notch1/genetics/*metabolismSignal Transduction/genetics/*physiology
Abstract
Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf(-/-) astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.
ISSN
0890-9369 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18676808

http://genesdev.cshlp.org/content/22/15/2028.full.pdf

http://hdl.handle.net/10371/67471
DOI
https://doi.org/10.1101/gad.1668708
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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