First published online December 20, 2005
Development 133, 204e (2006)
© The Company of Biologists Limited
Stem cell role for p53 puts theory to test
The `cancer stem cell hypothesis' proposes that some cancer cells have
properties of self-renewing stem cells. This prompted Jonas Frisén and
colleagues (see p. 363)
to investigate the role of a key tumour suppressor gene - p53 (which is
mutated in most tumours, particularly those in the brain) - in the renewal of
neural tissue stem cells. They discovered that cells of the brain's lateral
ventricle stem-cell niche overproliferate in p53-null mice, and that
p53 deficiency in `neurospheres' (clonal aggregates of neural stem cells in
vitro) results in increased renewal, owing to greater cell proliferation and
less apoptosis. Analysis of the neural stem cell transcriptome identified
several genes that are downregulated in p53-null neurospheres - most
conspicuously, p21 and p27, which are known to negatively regulate
proliferation in the lateral ventricle wall - leading the authors to speculate
that several pathways with roles in stem-cell renewal might converge on
p53.
Related articles in Development:
- p53 suppresses the self-renewal of adult neural stem cells
- Konstantinos Meletis, Valtteri Wirta, Sanna-Maria Hede, Monica Nistér, Joakim Lundeberg, and Jonas Frisén
Development 2006 133: 363-369.
[Abstract]
[Full Text]