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Cancer Res. 2008 Jun 15;68(12):4674-82. doi: 10.1158/0008-5472.CAN-07-6353.

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

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  • 1Department of Molecular and Cellular Biology, Graduate program in Translational Biology and Molecular Medicine, and Lester and Sue Smith Breast Center of Baylor College of Medicine, Houston, Texas, USA.


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.

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