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Tumorigenesis

Taking an alternative route

Nature Reviews Cancer volume 7, page 893 (2007)Cite this article

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Because BMI1 has INK4a- and ARF-independent functions in the brain and is involved in neural stem cell (NSC) proliferation and self-renewal, the authors examined the role of BMI1 in a mouse model of glioma. Either NSCs or astrocytes are used as the cell of origin for the disease, and tumours are induced by Cdkn2a deficiency in combination with retroviral expression of a constitutively active epidermal growth factor receptor (*EGFR). Cdkn2a−/−, but not Bmi1−/−;Cdkn2a−/−, primary astrocytes cultured in vitro undergo transformation when *EGFR is expressed. Furthermore, treatment with EGF or silencing of BMI1 using short hairpin RNA in Cdkn2a−/− cells has the same effect as *EGFR expression or Bmi1 knockout, respectively.

Most human gliomas express BMI1, but does BMI1 have a role in gliomagenesis in vivo? The authors observed an increase in the time to tumour development and prolonged survival of mice that were orthotopically transplanted with Bmi1−/−;Cdkn2a−/− primary astrocytes expressing *EGFR compared with Cdkn2a−/− astrocytes expressing *EGFR. The same result was observed when primary NSCs were injected rather than astrocytes. These data indicate that BMI1 is required for the development of gliomas and has functions that are independent of INK4a and ARF. However, there was a difference in the types of tumours that formed from Bmi1-null astrocytes and NSCs. Although grade IV tumours (glioblastoma multiforme (GBM)) arose from both Bmi1−/− and Bmi1+/+ astrocytes, Bmi1−/− NSCs never formed GBM, and the authors propose that this is because BMI1 has additional functions in NSCs that are required for the cells to become fully malignant.

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References

ORIGINAL RESEARCH PAPER

  1. Bruggeman, S. W. et al. Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma. Cancer Cell 12, 328–341 (2007)

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FURTHER READING

  1. Sparmann, A. & van Lohuizen, M. Polycomb silencers control cell fate, development and cancer. Nature Rev. Cancer 6, 846–856 (2006)

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Authors
  1. Sarah Seton-Rogers
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Seton-Rogers, S. Taking an alternative route. Nat Rev Cancer 7, 893 (2007). https://doi.org/10.1038/nrc2278

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  • DOI: https://doi.org/10.1038/nrc2278

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