Distinctive gene expression patterns in human mammary epithelial cells and breast 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 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 be 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.
Perou
C M
CM
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jeffrey
S S
SS
van de Rijn
M
M
Rees
C A
CA
Eisen
M B
MB
Ross
D T
DT
Pergamenschikov
A
A
Williams
C F
CF
Zhu
S X
SX
Lee
J C
JC
Lashkari
D
D
Shalon
D
D
Brown
P O
PO
Botstein
D
D
D000465:Algorithms; D001940:Breast / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D004798:Enzymes / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005810:Multigene Family; D011506:Proteins / Q000235:genetics*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004798:Enzymes; D011506:Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators