Abstract 3993: Stromal and epithelial microRNA signatures of early breast lesions linked to cancer progression

Abstract

Abstract Columnar cell hyperplasia (CCH) is considered to originate in normal terminal duct lobular units (TDLUs) and is potentially the first histologically identifiable alteration in the development of breast cancer. These lesions have been characterized to have a higher proliferation rate but the underlying mechanisms have not been studied. In order to detect early changes in breast cancer progression we therefore investigated microRNA (miRNA) expression profiles in TDLUs and CCH. Epithelial cells and surrounding stroma of TDLUs and CCH from formalin-fixed paraffin embedded tissue from four patients with high risk of developing breast cancer were laser capture microdissected and RNA was extracted. MiRNA expression profiles were obtained using a qRT-PCR-based array analyzing 667 human miRNAs. Interestingly, array analysis indicated substantial downregulation of several miRNAs in both the epithelial and the stromal compartments of CCH. MiRNA array analysis of paired samples from specimens with both TDLUs and CCH resulted in significant (p<0.05) decreased levels of 15 miRNAs in epithelial cells of CCH (miR-532-3p, miR-92a, miR-886-3p, let-7c, miR-150, miR-27a, miR-491-5p, miR-130a, miR-365, miR-886-5p, miR-204, miR-135a*, miR-494, miR-29c, miR-768-3p) and downregulation of 18 miRNAs in the stroma (miR-195, miR-296-5p, miR-99a, miR-100, miR-224, let-7c, miR-19b, miR-423-5p, miR-26a, miR-511, miR-128, miR-203, miR-30b, miR-374a, miR-374b, miR-29b, let-7e, miR-10a). We next downregulated miR-27a and miR-92a in a CCH derived cell line and observed a significantly increased proliferation. Opposite effect was observed when the miRs were overexpressed altogether suggesting a proliferative inhibitory function for the selected miRNAs. The miRNA signatures indicate concordant early changes in the epithelial and stromal compartment and the findings could be useful in identifying early key alterations in breast cancer progression that potentially could be targeted in novel prevention or treatment schedules. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3993. doi:10.1158/1538-7445.AM2011-3993