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Title:
Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors | Genome Biology
Description:
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-T 121 , TgMMTV-Wnt1, Brca1 Co/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.
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Keywords {🔍}
tumors, human, gene, expression, murine, pubmed, models, data, luminal, article, breast, google, scholar, tumor, genes, mouse, figure, cancer, analysis, samples, mammary, basallike, file, additional, cluster, group, groups, usa, subtype, cell, brca, showed, including, cells, intrinsic, features, high, mice, performed, central, analyses, normal, epithelial, expressed, significant, shared, list, perou, model, van,
Topics {✒️}
estrogen receptor alpha-positive cross-species gene-expression analysis heat-mediated epitope retrieval article number r76 article download pdf intrinsic list-based classifications prb-deficient/p53-deficient models genome-wide expression patterns mammary-specific model demonstrates precursor/stem cell population human data/gene lists related subjects terry van dyke & charles er-regulated gene cassette cell-type-specific responses top line-yellow group hierarchical clustering-based results no1-cn-05024/cn/nci gene expression profiling c57bl/6j mice leads high oncogenic h-ras mmtv-wnt-1 transgenic mice estrogen receptor status iruela-arispe ml kras2-linked genes prompted full size image repressing e-cadherin expression sv40 t-antigen mouse-human combined dataset human er-responsive genes intrinsic gene set authors’ original file wild-type mammary samples c-myc-induced tumorigenesis human breast cancers human 'claudin-low' tumors dr cam patterson tumor suppressor genes basal/myoepithelial gene clusters gene sets characteristic natl cancer inst poor clinical outcome van de rijn human her2+/er- tumors her2+/er- human tumors snow gb human her2+/er- subtype privacy choices/manage cookies supervised analysis method tgwap-myc 'spindloid' tumors
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headline:Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors
description: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. 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-T
121
, TgMMTV-Wnt1, Brca1
Co/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. 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.
datePublished:2007-05-10T00:00:00Z
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keywords:
Estrogen Receptor
Ionize Radiation
Additional Data File
Murine Tumor
Human Breast Tumor
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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headline:Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors
description: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. 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-T
121
, TgMMTV-Wnt1, Brca1
Co/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. 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.
datePublished:2007-05-10T00:00:00Z
dateModified:2007-05-10T00:00:00Z
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Estrogen Receptor
Ionize Radiation
Additional Data File
Murine Tumor
Human Breast Tumor
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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