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


CONCLUSIONS
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.
Huang
Shixia
S
Program in Cancer Biology and Genetics, Sloan-Kettering Institute, New York, NY 10021, USA. shixiah@bcm.tmc.edu
Li
Yi
Y
Chen
Yidong
Y
Podsypanina
Katrina
K
Chamorro
Mario
M
Olshen
Adam B
AB
Desai
Kartiki V
KV
Tann
Anne
A
Petersen
David
D
Green
Jeffrey E
JE
Varmus
Harold E
HE
D000818:Animals; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D005838:Genotype; D006965:Hyperplasia; D008321:Mammary Glands, Animal / Q000166:cytology / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D051155:Wnt1 Protein / Q000235:genetics*
D051155:Wnt1 Protein