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

Hye Min Jeon, Xun Jin, Joong Seob Lee, Se Yeong Oh, Young Woo Sohn, Hyo Jung Park, Min Joo Kyeung, Woong Yang Park, Do Hyun Nam, Ronald A. DePinho, Lynda Chin, Hyunggee Kim

Research output: Contribution to journalArticle

87 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2028-2033
Number of pages6
JournalGenes and Development
Volume22
Issue number15
DOIs
Publication statusPublished - 2008 Aug 1

Keywords

  • Cyclin E
  • Glioblastoma
  • Id4
  • Ink4a/Arf astrocyte
  • Neural stem-like cells
  • Notch signaling

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Jeon, H. M., Jin, X., Lee, J. S., Oh, S. Y., Sohn, Y. W., Park, H. J., Kyeung, M. J., Park, W. Y., Nam, D. H., DePinho, R. A., Chin, L., & Kim, H. (2008). Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling. Genes and Development, 22(15), 2028-2033. https://doi.org/10.1101/gad.1668708