Distinctive gene expression patterns in human mammary epithelial cells and breast cancers
Distinctive gene expression patterns in human mammary epithelial cells and breast cancers
复制标题
DOI：
10.1073/pnas.96.16.9212
复制
发表时间：
1999-08-03
影响因子：
11.1
通讯作者：
Botstein, D
中科院分区：
文献类型：
--
作者：
Perou, CM;Jeffrey, SS;Botstein, D
cDNA微阵列和聚类算法被用来识别在培养中生长的人乳腺上皮细胞和原发性人乳腺肿瘤中的基因表达模式。通过体外乳腺上皮细胞操作鉴定的共表达基因簇在乳腺肿瘤样品中的表达变化也显示出一致的模式。通过使用免疫组织化学与抗体对蛋白质编码的特定基因在一个集群中，肿瘤标本中的细胞类型的身份，有助于观察到的基因表达模式可以确定。培养细胞和乳腺肿瘤样本中具有一致表达模式的基因簇可能与样本中生物学变异的特定特征相关。发现两个这样的簇具有分别与细胞增殖速率的变化和与干扰素调节的信号转导途径的激活相关的模式。该分析还确定了乳腺肿瘤中基质细胞和淋巴细胞表达的基因簇。这些结果支持了这种系统方法的可行性和有用性，以研究人类癌症中基因表达模式的变异作为实体瘤的解剖和分类的手段。
cDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tumors. Clusters of coexpressed genes identified through manipulations of mammary epithelial cells in vitro also showed consistent patterns of variation in expression among breast tumor samples. By using immunohistochemistry with antibodies against proteins encoded by a particular gene in a cluster, the identity of the cell type within the tumor specimen that contributed the observed gene expression pattern could be determined. Clusters of genes with coherent expression patterns in cultured cells and in the breast tumors samples could he related to specific features of biological variation among the samples. Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the IFN-regulated signal transduction pathway, respectively. Clusters of genes expressed by stromal cells and lymphocytes in the breast tumors also were identified in this analysis. These results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors.