Authors

Jason I Herschkowitz, Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow
Karl Simin, Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USAFollow
Victor J Weigman, Department of Biology and Program in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow
Igor Mikaelian, The Jackson Laboratory, Bar Harbor, ME 04609, USAFollow
Jerry Usary, Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow
Zhiyuan Hu, Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow
Karen E Rasmussen, Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow
Laundette P Jones, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USAFollow
Shahin Assefnia, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USAFollow
Subhashini Chandrasekharan, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow
Michael G Backlund, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow
Yuzhi Yin, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USAFollow
Andrey I Khramtsov, Department of Pathology, University of Chicago, Chicago, IL 60637, USAFollow
Roy Bastein, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USAFollow
John Quackenbush, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USAFollow
Robert I Glazer, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USAFollow
Powel H Brown, Baylor College of Medicine, Houston, TX 77030, USAFollow
Jeffrey E Green, Transgenic Oncogenesis Group, Laboratory of Cancer Biology and Genetics. Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, MD 20892, USA. Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Section of Hematology/Oncology, Department of Medicine, Committees on Genetics and Cancer Biology, University of Chicago, Chicago, IL 60637, USA. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.Follow
Levy Kopelovich, Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, MD 20892, United States, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, United States, Section of Hematology/Oncology, Department of Medicine, Committees on Genetics and Cancer Biology, University of Chicago, Chicago, IL 60637, United States, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United StatesFollow
Priscilla A Furth, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USAFollow
Juan P Palazzo, Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, MD 20892, United States, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, United States, Section of Hematology/Oncology, Department of Medicine, Committees on Genetics and Cancer Biology, University of Chicago, Chicago, IL 60637, United States, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United StatesFollow
Olufunmilayo I Olopade, Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, MD 20892, United States, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, United StatesFollow
Philip S Bernard, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USAFollow
Gary A Churchill, The Jackson Laboratory, Bar Harbor, ME 04609, USAFollow
Terry Van Dyke, Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow
Charles M Perou, Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAFollow

Document Type

Article

Publication Date

1-1-2007

Comments

This article has been peer reviewed and is published in BMC Genome Biology Volume 8, Issue 5, 10 May 2007, Article number R76. The published version is available at DOI: 10.1186/gb-2007-8-5-r76. Copyright © BioMed Central Ltd.

Abstract

BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors. CONCLUSION: Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.