Distinctive gene expression patterns in human mammary epithelial cells andbreast cancers

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 t hrough manipulations of mammary epithelial cells in vitro also showed consi stent patterns of variation in expression among breast tumor samples. By us ing immunohistochemistry with antibodies against proteins encoded by a part icular gene in a cluster, the identity of the cell type within the tumor sp ecimen that contributed the observed gene expression pattern could be deter mined. Clusters of genes with coherent expression patterns in cultured cell s and in the breast tumors samples could he related to specific features of biological variation among the samples. Two such clusters were found to ha ve patterns that correlated with variation in cell proliferation rates and with activation of the IFN-regulated signal transduction pathway, respectiv ely. Clusters of genes expressed by stromal cells and lymphocytes in the br east tumors also were identified in this analysis. These results support th e feasibility and usefulness of this systematic approach to studying variat ion in gene expression patterns in human cancers as a means to dissect and classify solid tumors.