Abstract
Abstract In addition to mRNA gene expression profiling, miRNA expression analyses of human breast cancers have further demonstrated another layer of the molecular diversity of this disease and may potentially be a useful diagnostic and prognostic tool for breast cancer therapy and treatment. The development and use of relevant mouse models that closely reflect genetic alterations found in human breast cancers is critical to understand malignant progression in this disease and to test developmental therapeutics. The Mammary Tumour Virus (MMTV) Long Terminal Repeat (LTR) promoter-driven HER2/neu transgenic mouse model was developed to directly assess the effects of mammary gland specific expression of the neu protooncogene. Global miRNA expression profiling was performed on tumours derived from the MMTV-HER2/neu model. Normal mammary glands from FVB wild-type mice, HER2 overexpressing mammary glands from MMTV-HER2/neu transgenic mice and tumours derived from this model at different stages of the tumourigenic process were collected and microRNA expression profiling performed on them by Nanostring analysis. Differential expression of selected miRNAs, obtained by Nanostring screening, was further confirmed by quantitative Real Time analysis. By analyzing global miRNA expression profile on tissues collected from MMTV-HER2/neu mice at different stages of the tumourigenesis, we identified significant differences in miRNA expression patterns between tumours and normal mammary tissue and between non-metastatic and metastatic tumours. miRNA expression characterization of tumours at various stages of development along with gene expression in mouse models would profoundly enhance our knowledge of progressive genetic changes associated with oncogene-induced events in breast cancer. Citation Format: Claudia Piovan, Gianpiero Di Leva, Douglas Cheung, Matteo Fassan, Arpan Kumar, Dario Palmieri, Marilena V. Iorio, Carlo M. Croce. MicroRNA expression profiling in MMTV-neu breast cancer mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 530. doi:10.1158/1538-7445.AM2014-530
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