Gene expression profiling of NMU-induced rat mammary tumors: cross species comparison with human breast cancer
Gene expression profiling of NMU-induced rat mammary tumors: cross species comparison with human breast cancer
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DOI：
10.1093/carcin/bgi100
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发表时间：
2005-08-01
期刊：
影响因子：
4.7
通讯作者：
Miron, PL
中科院分区：
文献类型：
--
作者：
Chan, MM;Lu, X;Miron, PL
乳腺癌是一种复杂的遗传性疾病，其特征是多个分子改变的累积。大鼠诱发的NMU乳腺癌模型是用于研究乳腺癌发生的，因为它与人类乳腺疾病非常相似。为了从更全球的分子角度评估该模型的有效性，并设计出一种通用技术来比较动物特征和人类微阵列研究，我们使用免疫组织化学和微阵列分析相结合的方法对25个NMU诱导的乳腺肿瘤和11个正常腺体进行了表征。大鼠乳腺癌被归类为非侵袭性、ER阳性的导管癌，由分化的上皮细胞和肌上皮细胞组成。使用包含15866个基因的大鼠Affymetrix阵列生成的基因表达谱表明，大鼠乳腺肿瘤是同源的，H-ras突变不具有独特的分子特征。我们通过合并原始微阵列数据，使用一种结合了跨物种和跨平台分析的方法，将所得到的老鼠图谱与从人类数据集中获得的图谱进行了比较。使用这一新的策略，我们展示了2305个大鼠同源基因概括人类肿瘤分类的能力，这些分类来自人类Affymetrix阵列。NMU诱导的原发肿瘤的基因表达谱与ER阳性、低至中等级别的乳腺癌最为相似。我们的技术提供了一种方法，将癌症动物模型的基因表达数据与人类癌症和疾病状态相关联。
Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The NMU breast cancer model induced in the rat is used for the study of mammary carcinogenesis because it closely mimics human breast disease. To assess the validity of this model from a more global molecular perspective, and also to devise a general technique to compare animal profiles with human microarray studies, we have characterized 25 NMU-induced mammary tumors and 11 normal glands using a combination of immunohistochemical and microarray analyses. The rat mammary carcinomas were classified as non-invasive, ER-positive ductal carcinomas with a composition of differentiated epithelial and myoepithelial cell lineages. Gene expression profiles generated using rat Affymetrix arrays containing 15 866 genes demonstrated that the rat mammary tumors are homogeneous and that H-ras mutations did not confer a unique molecular signature. We compared the resulting rat profiles with those obtained from a human dataset by merging the raw microarray data, using an approach that involves a combination of cross-species and cross-platform analysis. Using this novel strategy, we demonstrate the ability of 2305 rat orthologs to recapitulate the classification of human tumors derived from human Affymetrix arrays. The gene expression profiles of the NMU-induced primary tumors were most similar to ER-positive, low to intermediate grade breast cancer. Our technique provides a means to correlate gene expression data from animal models of cancer to human cancer and disease states.