Gene expression in murine mammary epithelial stem cell-like cells shows similarities to human breast cancer gene expression.
BACKGROUND
Mammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized. Breast tumors can be divided into subgroups, each one requiring specific treatment. To determine a possible association between mammary stem cells and breast cancer, a detailed characterization of the transcriptome in mammary stem cells is essential.


METHODS
We have used a murine mammary epithelial stem-like cell line (HC11) and made a thorough investigation of global gene-expression changes during stepwise differentiation using dual-color comparative microarray technique. Subsequently, we have performed a cross-species comparison to reveal conserved gene expression between stem cells and subtype-specific and prognosis gene signatures, and correlated gene expression to in vivo mammary gland development.


RESULTS
Our analysis of mammary stem-like and stepwise cell differentiation, and an in-depth description of our findings in a breast cancer perspective provide a unique map of the transcriptomic changes and a number of novel mammary stem cell markers. We correlate the alterations to in vivo mammary gland differentiation, and describe novel changes in nuclear receptor gene expression. Interestingly, our comparisons show that specific subtypes of breast cancers with poor prognosis and metastasizing capabilities show resemblance to stem-like gene expression.


CONCLUSIONS
The transcriptional characterization of these mammary stem-like cells and their differentiation-induced gene expression patterns is here made widely accessible and provides a basis for research on mammary stem-like cells. Our comparisons suggest that some tumors are more stem-like than others, with a corresponding worse prognosis. This information would, if established, be important for treatment decisions. We also suggest several marker candidates valuable to investigate further.
Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3013 Science & Engineering Research Center, Houston, TX 77204, USA. ceciliawilliams@uh.edu
Cecilia
C
Williams
Luisa
L
Helguero
Karin
K
Edvardsson
Lars-Arne
LA
Haldosén
Jan-Ake
JA
Gustafsson
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000166:cytology