p53 suppresses the self-renewal of adult neural stem cells.
There is increasing evidence that tumors are heterogeneous and that a subset of cells act as cancer stem cells. Several proto-oncogenes and tumor suppressors control key aspects of stem cell function, suggesting that similar mechanisms control normal and cancer stem cell properties. We show here that the prototypical tumor suppressor p53, which plays an important role in brain tumor initiation and growth, is expressed in the neural stem cell lineage in the adult brain. p53 negatively regulates proliferation and survival, and thereby self-renewal, of neural stem cells. Analysis of the neural stem cell transcriptome identified the dysregulation of several cell cycle regulators in the absence of p53, most notably a pronounced downregulation of p21 expression. These data implicate p53 as a suppressor of tissue and cancer stem cell self-renewal.
Meletis
Konstantinos
K
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Wirta
Valtteri
V
Hede
Sanna-Maria
SM
Nistér
Monica
M
Lundeberg
Joakim
J
Frisén
Jonas
J
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D016158:Genes, p53; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53