Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.
Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.
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DOI：
10.1186/gb-2007-8-5-r76
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Perou CM
中科院分区：
文献类型：
--
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
比较乳腺肿瘤基因表达谱从13个小鼠模型，使用微阵列和人类乳腺肿瘤显示，许多定义的特征，人类亚型之间的小鼠模型是保守的。尽管已经开发了许多乳腺癌小鼠模型，但我们不知道任何一种模型在多大程度上忠实地代表了临床上显著的人类表型。为了满足这一需求，我们使用DNA微阵列表征了13种不同小鼠模型的乳腺肿瘤基因表达谱，并将所得数据与人类乳腺肿瘤的数据进行了比较。无监督的层次聚类分析显示，六种模型（TgWAP-Myc、TgMMTV-Neu、TgMMTV-PyMT、TgWAP-Int 3、TgWAP-Tag和TgC 3（1）-Tag）产生的肿瘤在每个菌株内具有独特和同质的表达模式。然而，在其他四种模型（TgWAP-T121、TgMMTV-Wnt 1、Brca 1Co/Co、TgMMTV-Cre、p53+/-和DMBA诱导）中，均出现了具有各种组织学和表达谱的肿瘤。在许多模型中，认识到与人类乳腺肿瘤的相似性，包括增殖和人类乳腺肿瘤亚型特征。值得注意的是，几种模型的肿瘤显示出人类基底样乳腺肿瘤的特征，包括两种诱导Brca 1缺陷的模型。其他小鼠模型的肿瘤具有与人管腔肿瘤相同的特征并倾向于基因富集的意义;然而，这些小鼠肿瘤缺乏雌激素受体（ER）和ER调节基因的表达。TgMMTV-Neu肿瘤与人HER 2 +/ER-亚型没有显著的基因重叠，并且与人管腔肿瘤更相似。人类亚型的许多定义特征在小鼠模型中是保守的。虽然没有单一的小鼠模型概括了给定的人亚型的所有表达特征，但这些共有的表达特征为鼠乳腺肿瘤模型与人乳腺肿瘤的改善整合提供了共同的框架。
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. 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-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. 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.