RNAi as a Routine Route Toward Breast Cancer Therapy
Final rept. 1 Sep 2008-28 Feb 2014
COLD SPRING HARBOR LAB NY
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During the first year of this innovator award, we made significant progress toward two of our aims. We constructed a third generation RNAi library and made that available to the breast cancer community. This resource has nearly 75,000 independent, sequence verified clones targeting 18,000 human genes. A similar library for the mouse genome is nearing completion. We also scaled up our shRNA screening platform in preparation for lethality surveys of all suitable and available BC cell lines, including matched pairs of lines that have acquired resistance to herceptin in vitro. Relevant to our second aim, we have profiled microRNA from each of the identifiable epithelial cell types in the mouse mammary gland and are undertaking similar efforts in human. The goal is to develop microRNA sensor strategies that will permit visualization of each cell type in vivo and enable their isolation and manipulation in vitro. Finally, we showed that two microRNAs, let-7 and miR-93, can deplete tumor initiating cells from a number of basal breast cancer cell lines.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research