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

Yang,Jianmin; Yu,Haijing; Zhang,Liang; Deng,Hua; Wang,Qi; Li,Wenping; Zhang,Anqin; Gao,Hongyi; Yin,Aihua

doi:10.3892/or.2015.4523

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

Authors:
- Jianmin Yang
- Haijing Yu
- Liang Zhang
- Hua Deng
- Qi Wang
- Wenping Li
- Anqin Zhang
- Hongyi Gao
- Aihua Yin
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Affiliations: Breast Disease Center, Guangdong Women and Children's Hospital, Guangzhou, Guangdong 511400, P.R. China, Translational Medicine Center, Guangdong Women and Children's Hospital, Guangzhou, Guangdong 511400, P.R. China, Department of Pathology, Guangdong Women and Children's Hospital, Guangzhou, Guangdong 511400, P.R. China, Medical Genetics Center, Guangdong Women and Children's Hospital, Guangzhou, Guangdong 511400, P.R. China
Published online on: December 28, 2015 https://doi.org/10.3892/or.2015.4523
Pages: 1689-1695

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Abstract

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.

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