Overexpressed genes associated with hormones in terminal ductal lobular units identified by global transcriptome analysis: An insight into the anatomic origin of breast cancer.

Although human breast ducts and terminal ductal lobular units (TDLUs) share the same cell types, ample evidence shows that TDLUs are the predominant site for the origin of breast cancer. Yet, there is still limited information concerning the molecular mechanisms. Analysis of transcriptomic profiles in TDLUs may provide insight into early breast tumorigenesis. We compared genome-wide expression profiles of 8 matched sets of breast main duct and TDLU samples, using significance analysis of microarray (SAM) software to screen differentially expressed genes (DEGs) with fold-change >2.0 and q-value <0.05. Moreover, we used Gene Ontology for functional enrichment analysis. We identified 472 DEGs between the two tissue types, and confirmed 17 randomly chosen DEGs by quantitative reverse transcription-PCR (qRT-PCR). Notably, hormone-related pathways were highly enriched in the TDLU samples, including various hormone-related DEGs that are associated with breast carcinogenesis and tumor progression. Oncogenic upregulation in TDLUs indicates a potential inappropriate or excessive response to successive hormone stimulus during the proliferation, differentiation and lactation cycles of the human mammary gland. Imbalanced hormone reactions may finally result in the early onset of neoplastic transformation that occurs mostly in breast TDLUs.