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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • CD24 Antigen / metabolism
  • Cell Line, Tumor
  • Cell Transplantation
  • Colony-Forming Units Assay
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Homozygote
  • Immunoenzyme Techniques
  • Integrin beta1 / metabolism
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neoplastic Stem Cells*
  • Nucleotidyltransferases / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Tumor Suppressor Protein p53 / physiology*


  • Biomarkers, Tumor
  • CD24 Antigen
  • Integrin beta1
  • Tumor Suppressor Protein p53
  • Nucleotidyltransferases
  • lincosaminide O-nucleotidyltransferase