Discovery of Metastatic Breast Cancer Suppressor Genes Using Functional Genome Analysis
DANA-FARBER CANCER INST BOSTON MA
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I hypothesize that metastasis is governed by specific genetic alterations and that identifying this genetic program will provide candidates for new therapeutic targets. My aim is to discover potential metastasis suppressor genes MSGs in murine model of breast cancer metastasis through genome scale loss-of-function studies. As a first step to establish a system for prescreening candidate MSGs among the vast number of gene candidates, I calibrated two in vitro tumor invasion assays, metastasis initiation assay and Matrigel invasion assay. Especially, the Matrigel transwell assay has superior robustness that allow me to further develop assay in both arrayed and pooled format. In parallel, I have pursued an in vivo strategy to identify metastasis-related genes using an in vivo cell type-specific lentiviral gene delivery system. I first confirmed that this gene delivery system efficiently permits gene expression in an in vitro cell culture model. Next, I tested the lentiviral gene delivery system in an in vivo subcutaneous tumor model. Virus was introduced through tail vein injection offers reasonable virus delivery efficiency. I am currently testing this in a murine model of tumor formation.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research