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

Abstract

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.

• Authors: Mei Zhang, Fariba Behbod, Rachel L Atkinson, Melissa D Landis, Frances Kittrell, David Edwards, Daniel Medina, Anna Tsimelzon, Susan Hilsenbeck, Jeffrey E Green, Aleksandra M Michalowska, Jeffrey M Rosen
• Journal: Cancer research (Cancer Res) Vol. 68 Issue 12 Pg. 4674-82 (Jun 15 2008) ISSN: 1538-7445 [Electronic] United States
• PMID: 18559513 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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