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

被引：565

作者：

Cicalese, Angelo ^{[1
]}

Bonizzi, Giuseppina ^{[1
]}

Pasi, Cristina E. ^{[1
]}

Faretta, Mario ^{[1
]}

Ronzoni, Simona ^{[1
]}

Giulini, Barbara ^{[1
]}

Brisken, Cathrin ^{[3
]}

Minucci, Saverio ^{[1
,4
]}

Di Fiore, Pier Paolo ^{[1
,2
,4
]}

Pelicci, Pier Giuseppe ^{[1
,4
]}

机构：

[1] IEO, Dept Expt Oncol, I-20139 Milan, Italy

[2] Fdn Ist FIRC Oncol Mol IFOM, I-20139 Milan, Italy

[3] Swiss Inst Expt Canc Res, Natl Ctr Competence Res Mol Oncol, Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland

[4] Univ Milan, Dipartimento Med Chirurg & Odontoiatria, I-20122 Milan, Italy

来源：

CELL | 2009年 / 138卷 / 06期

关键词：

IN-VIVO; MOUSE; RESTORATION; CANCER; MODEL; GLAND; MICE; ACTIVATION; PATHWAY;

D O I：

10.1016/j.cell.2009.06.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1083 / 1095

页数：13

共 29 条

[1] Fitting limiting dilution experiments with generalized linear models results in a test of the single-hit Poisson assumption [J].