Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors Public Deposited

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  • Van Dyke, Terry A.
    • Affiliation: School of Medicine, Department of Genetics, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Backlund, Michael G
    • Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
  • Furth, Priscilla A
    • Other Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
  • Kopelovich, Levy
    • Other Affiliation: Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, MD 20892, USA
  • Chandrasekharan, Subhashini
    • Affiliation: School of Medicine, Department of Genetics
  • Mikaelian, Igor
    • Other Affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA
  • Palazzo, Juan P
    • Other Affiliation: Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA
  • Glazer, Robert I
    • Other Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
  • Rasmussen, Karen E
    • Affiliation: School of Medicine, Department of Genetics, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Churchill, Gary A
    • Other Affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA
  • Weigman, Victor J
    • Affiliation: College of Arts and Sciences, Department of Biology, School of Medicine
    • Other Affiliation: Curriculum in Bioinformatics and Computational Biology
  • Bernard, Philip S
    • Other Affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
  • Green, Jeffrey E
    • Other Affiliation: Transgenic Oncogenesis Group, Laboratory of Cancer Biology and Genetics
  • Bastein, Roy
    • Other Affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
  • Simin, Karl
    • Other Affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
  • Usary, Jerry
    • Affiliation: School of Medicine, Department of Genetics, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Perou, Charles
    • Affiliation: School of Medicine, Department of Genetics, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Brown, Powel H
    • Other Affiliation: Baylor College of Medicine, Houston, TX 77030, USA
  • Quackenbush, John
    • Other Affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
  • Herschkowitz, Jason I
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine, Curriculum in Genetics and Molecular Biology
  • Assefnia, Shahin
    • Other Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
  • Hu, Zhiyuan
    • Affiliation: School of Medicine, Department of Genetics, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Khramtsov, Andrey I
    • Other Affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA
  • Jones, Laundette P
    • Other Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
  • Olopade, Olufunmilayo I
    • Other Affiliation: Section of Hematology/Oncology, Department of Medicine, Committees on Genetics and Cancer Biology, University of Chicago, Chicago, IL 60637, USA
  • Yin, Yuzhi
    • Other Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
Abstract
  • 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.
Date of publication
Identifier
  • doi:10.1186/gb-2007-8-5-r76
  • 17493263
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Jason I Herschkowitz et al.; licensee BioMed Central Ltd.
License
Journal title
  • Genome Biology
Journal volume
  • 8
Journal issue
  • 5
Page start
  • R76
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1465-6906
Bibliographic citation
  • Genome Biology. 2007 May 10;8(5):R76
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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