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Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice

Shixia Huang123*, Yi Li124, Yidong Chen5, Katrina Podsypanina1, Mario Chamorro1, Adam B Olshen6, Kartiki V Desai78, Anne Tann2, David Petersen7, Jeffrey E Green7 and Harold E Varmus1

Author Affiliations

1 Program in Cancer Biology and Genetics, Sloan-Kettering Institute, New York, NY 10021, USA

2 Breast Center, Baylor College of Medicine, Houston, TX 77030, USA

3 Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA

4 Department of Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA

5 National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA

6 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA

7 National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

8 Johns Hopkins in Singapore Ltd, The Nanos, Singapore 138669, Republic of Singapore

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Genome Biology 2005, 6:R84  doi:10.1186/gb-2005-6-10-r84

Published: 30 September 2005

Abstract

Background

In human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ, invasive cancer, and metastasis. The changes in gene expression associated with this stepwise progression are unclear. Mice transgenic for mouse mammary tumor virus (MMTV)-Wnt-1 exhibit discrete steps of mammary tumorigenesis, including hyperplasia, invasive ductal carcinoma, and distant metastasis. These mice might therefore be useful models for discovering changes in gene expression during cancer development.

Results

We used cDNA microarrays to determine the expression profiles of five normal mammary glands, seven hyperplastic mammary glands and 23 mammary tumors from MMTV-Wnt-1 transgenic mice, and 12 mammary tumors from MMTV-Neu transgenic mice. Adipose tissues were used to control for fat cells in the vicinity of the mammary glands. In these analyses, we found that the progression of normal virgin mammary glands to hyperplastic tissues and to mammary tumors is accompanied by differences in the expression of several hundred genes at each step. Some of these differences appear to be unique to the effects of Wnt signaling; others seem to be common to tumors induced by both Neu and Wnt-1 oncogenes.

Conclusion

We described gene-expression patterns associated with breast-cancer development in mice, and identified genes that may be significant targets for oncogenic events. The expression data developed provide a resource for illuminating the molecular mechanisms involved in breast cancer development, especially through the identification of genes that are critical in cancer initiation and progression.