Discovery of Metastatic Breast Cancer Suppressor Genes Using Functional Genome Analysis.

摘要

To identify metastatic suppressor genes (MSGs), I proposed to perform genome-scale genetic perturbation using lentiviral delivered shRNA library in a mouse model of breast cancer metastasis and an in vitro metastasis assay. To enhance the screening throughput and robustness of the mouse metastasis model, I calibrated an ALSV-based lentiviral gene delivery system. This system achieved reasonable virus delivery efficiency in vitro and to subcutaneously formed tumor in vivo. However, it failed to delivery genes to primary breast tumor in vivo. In parallel, I generated list of candidate MSGs and tested the shRNAs for selected candidate for pilot screen in vivo. The MSGs includes known/putative MSGs through literature research and genes that is essential specific to metastatic breast cancer cell lines. Further experiment is on going to use the candidate list to calibrate the in vivo and in vitro metastasis assay systems.