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REPORT DATE (DD-MM-YYYY)May 2014 (From -To) 1Sep2008-28Feb2014
REPORT TYPE
Final
DATES COVERED
TITLE AND SUBTITLERNAi as a Routine Route Toward Breast Cancer Therapy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0572 5c. PROGRAM ELEMENT NUMBER
AUTHOR(S)Gregory J. Hannon, PhD.
5d. PROJECT NUMBERemail: hannon@cshl.edu 5e. TASK NUMBER 5f. WORK UNIT NUMBER
PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERCold Spring Harbor Laboratory One Bungtown Road Cold Spring Harbor, NY 11724
SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)US Army Medical Research and Materiel Command Fort Detrick, MA 21702
SPONSOR/MONITOR'S REPORT NUMBER(S)
DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited
SUPPLEMENTARY NOTES
ABSTRACTDuring 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.
SUBJECT TERMS
INTRODUCTIONThe goal of this innovator award is to continue to develop and apply RNAi-based screening methods to discover new routes toward breast cancer therapy. The project has three sets of goals. First is to integrate genomic and geneti...