Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas

@article{Leung2004Bmi1IE,
  title={Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas},
  author={Carly Leung and Merel Lingbeek and Olga Shakhova and James Liu and Ellen Tanger and Parvin Saremaslani and Maarten van Lohuizen and Silvia Marino},
  journal={Nature},
  year={2004},
  volume={428},
  pages={337-341}
}
Overexpression of the polycomb group gene Bmi1 promotes cell proliferation and induces leukaemia through repression of Cdkn2a (also known as ink4a/Arf) tumour suppressors. Conversely, loss of Bmi1 leads to haematological defects and severe progressive neurological abnormalities in which de-repression of the ink4a/Arf locus is critically implicated. Here, we show that Bmi1 is strongly expressed in proliferating cerebellar precursor cells in mice and humans. Using Bmi1-null mice we demonstrate a… 

Bmi1 overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation

BMI1 overexpression in GCP-derived human medulloblastomas probably occurs during later stages of oncogenesis and might serve to enhance tumour cell survival, and data suggest that different levels and timing of Bmi1 overeexpression yield distinct cellular outcomes within the same cellular lineage.

GFAP-Cre-Mediated Transgenic Activation of Bmi1 Results in Pituitary Tumors

Two conditional Bmi1 transgenic models that were crossed with GFAP-Cre mice to activate transgenic expression resulted in pituitary tumors but was insufficient to induce medulloblastoma therefore indicating that the oncogenic function of Bmi 1 depends on regulation of p16INK4A/Rb rather than onregulation of p19ARF/p53.

Sonic hedgehog regulates Bmi1 in human medulloblastoma brain tumor-initiating cells

Findings implicate Bmi1 and Hh as mutually indispensable pathways in medulloblastoma BTIC maintenance and propose that the BTIC marker CD133 may segregate a cell population with a Hh-receptor phenotype, thus demonstrating a cell–cell interaction between the CD133+ Hh receptor cells and theCD133− HH-secreting cells.

Bmi1 is required for Hedgehog pathway-driven medulloblastoma expansion.

The first demonstration that Bmi1 is required for spontaneous de novo development of a solid tumor arising in the brain is provided, and a crucial role for Bmi 1-dependent, nestin-expressing progenitor cells in medulloblastoma expansion is suggested.

p27Kip1, a double-edged sword in Shh-mediated medulloblastoma

The data indicate that the dosage of p27Kip1 plays a role in cell cycle progression and tumor suppression in Shh-mediated medulloblastoma expansion and it is found that mis-localized p27kip1 may play a positive role in motility in medullOBlastoma cells.

Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma

Bmi1 Loss Produces an Increase in Astroglial Cells and a Decrease in Neural Stem Cell Population and Proliferation

Bmi1 is expressed in the germinal zone in vivo and in NSCs as well as in progenitors proliferating in vitro, but not in differentiated cells, and the altered cell pattern of the Bmi1-/- brain shows that in vivo astrocyte precursors can proliferate in the absence of Bmi 1.

Genome-wide analysis of gene expression and alternative splicing in human medulloblastoma

Interestingly, Shh-treated GCPs recapitulated the splicing patterns observed in the tumour samples for six out of the eight genes analysed, suggesting that the preferential expression of specific transcript forms is regulated during normal cerebellar development.

Disruption of the PACAP gene promotes medulloblastoma in ptc1 mutant mice.

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