This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhang, M. Articles by Rosen, J. M. PubMed PubMed Citation Articles by Zhang, M. Articles by Rosen, J. M.

Identification of Tumor-Initiating Cells in a p53-Null Mouse Model of Breast Cancer

¹ Department of Molecular and Cellular Biology, ² Graduate program in Translational Biology and Molecular Medicine, and ³ Lester and Sue Smith Breast Center of Baylor College of Medicine, Houston, Texas and ⁴ Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland

Requests for reprints: Jeffrey M. Rosen, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3498. Phone: 713-798-6210; Fax: 713-798-8012; E-mail: jrosen{at}bcm.edu.

Key Words: breast cancer • p53 null mouse model • tumor-initiating cells

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^HCD24^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^HCD24^H subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin^–CD29^HCD24^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. [Cancer Res 2008;68(12):4674–82]