Identification of tumor-initiating cells in a p53-null mouse model of breast cancer

被引:248
作者
Zhang, Mei
Behbod, Fariba
Atkinson, Rachel L.
Landis, Melissa D.
Kittrell, Frances
Edwards, David
Medina, Daniel
Tsimelzon, Anna
Hilsenbeck, Susan
Green, Jeffrey E. [1 ]
Michalowska, Aleksandra M. [1 ]
Rosen, Jeffrey M.
机构
[1] NCI, Canc Biol Lab, Bethesda, MD 20892 USA
关键词
D O I
10.1158/0008-5472.CAN-07-6353
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin-CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. Furthermore, this p53-null mouse mammary tumor model may allow us to identify new CSC markers and to test the functional importance of these markers.
引用
收藏
页码:4674 / 4682
页数:9
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