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Cancer Research 68, 4674, June 15, 2008. doi: 10.1158/0008-5472.CAN-07-6353
© 2008 American Association for Cancer Research

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Cell, Tumor, and Stem Cell Biology

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

Mei Zhang1, Fariba Behbod1, Rachel L. Atkinson1,2, Melissa D. Landis3, Frances Kittrell1, David Edwards1, Daniel Medina1, Anna Tsimelzon3, Susan Hilsenbeck3, Jeffrey E. Green4, Aleksandra M. Michalowska4 and Jeffrey M. Rosen1

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 LinCD29HCD24H 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 LinCD29HCD24H subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the LinCD29HCD24H 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]




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.