The Tumor Suppressor p53 Regulates Polarity of Self-Renewing Divisions in Mammary Stem Cells

Stem-like cells may be integral to the development and maintenance of human cancers. Direct proof is still lacking, mainly because of our poor understanding of the biological differences between normal and cancer stem cells (SCs). Using the ErbB2 transgenic model of breast cancer, we found that self...

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Bibliographic Details
Published in:Cell 2009-09, Vol.138 (6), p.1083-1095
Main Authors: Cicalese, Angelo, Bonizzi, Giuseppina, Pasi, Cristina E., Faretta, Mario, Ronzoni, Simona, Giulini, Barbara, Brisken, Cathrin, Minucci, Saverio, Di Fiore, Pier Paolo, Pelicci, Pier Giuseppe
Format: Article
Language:English
Subjects:
Animals
Cell Division
Cell Polarity
DEVBIO
Female
Humans
HUMDISEASE
Mammary Neoplasms, Animal - metabolism
Mice
Mice, Transgenic
Neoplastic Stem Cells - cytology
Neoplastic Stem Cells - metabolism
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - metabolism
STEMCELL
Tumor Suppressor Protein p53 - metabolism
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Summary:Stem-like cells may be integral to the development and maintenance of human cancers. Direct proof is still lacking, mainly because of our poor understanding of the biological differences between normal and cancer stem cells (SCs). Using the ErbB2 transgenic model of breast cancer, we found that self-renewing divisions of cancer SCs are more frequent than their normal counterparts, unlimited and symmetric, thus contributing to increasing numbers of SCs in tumoral tissues. SCs with targeted mutation of the tumor suppressor p53 possess the same self-renewal properties as cancer SCs, and their number increases progressively in the p53 null premalignant mammary gland. Pharmacological reactivation of p53 correlates with restoration of asymmetric divisions in cancer SCs and tumor growth reduction, without significant effects on additional cancer cells. These data demonstrate that p53 regulates polarity of cell division in mammary SCs and suggest that loss of p53 favors symmetric divisions of cancer SCs, contributing to tumor growth.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2009.06.048