Bmi1 controls tumor development in an ink4a/Arf-independent manner in a mouse model for glioma

Sophia W. M. Bruggeman, Danielle Hulsman, Ellen Tanger, Tessa Buckle, Marleen Blom, John Zevenhoven, Olaf van Tellingen, Maarten van Lohuizen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

248 Citations (Scopus)

Abstract

The Polycomb group and oncogene Bmi1 is required for the proliferation of various differentiated cells and for the self-renewal of stem cells and leukemic cancer stem cells. Repression of the Ink4alArf locus is a well described mechanism through which Bmi1 can exert its proliferative effects. However, we now demonstrate in an orthotopic transplantation model for glioma, a type of cancer harboring cancer stem cells, that Bmi1 is also required for tumor development in an Ink4alArfindependent manner. Tumors derived from Bmi1;Ink4alArf doubly deficient astrocytes or neural stem cells have a later time of onset and different histological grading. Moreover, in the absence of Ink4alArf, Bmi1-deficient cells and tumors display changes in differentiation capacity.

Original languageEnglish
Pages (from-to)328-341
Number of pages14
JournalCancer cell
Volume12
Issue number4
DOIs
Publication statusPublished - Oct-2007
Externally publishedYes

Keywords

  • NEURAL STEM-CELL
  • GROWTH-FACTOR RECEPTOR
  • ACUTE MYELOID-LEUKEMIA
  • MYC TRANSGENIC MICE
  • III BETA-TUBULIN
  • SELF-RENEWAL
  • PLEOMORPHIC XANTHOASTROCYTOMA
  • NEUROBLASTOMA-CELLS
  • BRAIN-TUMORS
  • CANCER-CELLS

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