Roles of miRNAs in breast cancer stem cells, drug sensitivity, and spontaneous metastases in orthotopic human-in-mouse models.

1082 Background: Our previous work showed that breast cancer stem cells (BCSCs) contribute to spontaneous metastasis and BCSCs were enriched in CD44+ cells from both primary tumors and lung metastases. We hypothesize that microRNAs (miRNAs) play important roles in breast cancer progression and chemotherapy response. Methods: To characterize miRNAs important for breast cancer progression and chemotherapy response, we generated breast tumor metastasis models, improved imaging and monitoring of breast tumor in vivo, profiled miRNAs of breast tumors, and screened miRNAs that regulate invasion and drug response. To identify miRNA target genes, we combined multiple algorithms prediction, mRNA analysis, westerns, luciferase assays and functional rescue experiments. Results: With clinical breast tumor specimens, we developed human-in-mouse breast tumor models with spontaneous metastases and transduced BCSCs with optimized fusion genes (Luc2-eGFP or –tdTomato), which enabled both bioluminescence imaging (BLI) and ...