Transcriptomes of breast epithelium and stroma in normal reduction mammoplasty and invasive breast cancer patients.

The molecular basis of breast cancer invasion and metastasis is not well understood. Our objective was to analyze transcriptome differences between stromal and epithelial cells in normal breast tissue and invasive breast cancer to define the role stroma plays in invasion. Total RNA was isolated from epithelial and stromal cells that were laser captured from normal breast tissue (n=5) and invasive breast cancer (n=28). Gene expression was measured using Affymetrix U133A 2.0 GeneChips. Differential gene expression was evaluated and compared within a model that accounted for cell type (epithelial [E] versus stromal [S]), diagnosis (cancer [C] versus normal [N]) as well as cell type-diagnosis interactions. Compared to NE, the CE transcriptome was highly enriched with genes in proliferative, motility and ECM ontologies. Differences in CS and NS transcriptomes suggested that the ECM was being remodeled in invasive breast cancer, as genes were over-represented in ECM and proteolysis ontologies. Genes more highly expressed in CS compared to CE were primarily ECM components or were involved in the remodeling of ECM, suggesting that ECM biosynthesis and remodeling were initiated in the tumor stromal compartment.

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Casey T, Bond J, Tighe S, Hunter T, Lintault L, Patel O, Eneman J, Crocker A, White J, Tessitore J, Stanley M, Harlow S, Weaver D, Muss H, Plaut K