The `cancer stem cell hypothesis' proposes that some cancer cells have properties of self-renewing stem cells. This prompted Jonas Frisén and colleagues (see )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.
