Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors
Autor: | Juan P. Palazzo, John Quackenbush, Karen E. Rasmussen, Yuzhi Yin, Subhashini Chandrasekharan, Levy Kopelovich, Zhiyuan Hu, Gary A. Churchill, Andrey Khramtsov, Jeffrey E. Green, Charles M. Perou, Jason I. Herschkowitz, Olufunmilayo I. Olopade, Laundette P. Jones, Powel H. Brown, Victor J. Weigman, Igor Mikaelian, Michael G. Backlund, Philip S. Bernard, Priscilla A. Furth, Roy Bastein, Robert I. Glazer, Karl Simin, Jerry Usary, Terry Van Dyke, Shahin Assefnia |
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Jazyk: | angličtina |
Předmět: |
Aging
Bioinformatics Breast Neoplasms Biology 03 medical and health sciences Mice Experimental 0302 clinical medicine Species Specificity Information and Computing Sciences Breast Cancer Gene expression Genetics 2.1 Biological and endogenous factors Animals Humans Cluster Analysis Aetiology Cancer 030304 developmental biology Oligonucleotide Array Sequence Analysis Regulation of gene expression 0303 health sciences Mammary tumor Neoplastic Research Gene Expression Profiling Mammary Neoplasms Mammary Neoplasms Experimental Biological Sciences Claudin-Low Phenotype Molecular biology Human genetics Neoplasm Proteins Gene expression profiling Gene Expression Regulation Neoplastic Gene Expression Regulation 030220 oncology & carcinogenesis Cancer research DNA microarray Environmental Sciences |
Zdroj: | Genome biology, vol 8, iss 5 Genome Biology |
ISSN: | 1465-6906 |
DOI: | 10.1186/gb-2007-8-5-r76 |
Popis: | Comparison of mammary tumor gene-expression profiles from thirteen murine models using microarrays and with that of human breast tumors showed that many of the defining characteristics of human subtypes were conserved among mouse models. 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. |
Databáze: | OpenAIRE |
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