Genomic Approaches for Detection and Treatment of Breast Cancer
Annual rept. 1 Jul 2006-30 Jun 2007
BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
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A key part of our research plan has been the development and use of retroviral vectors expressing RNA interference RNAs to identify human genes involved in causing or restraining cancer. In our first progress reports we described our efforts to develop shRNA libraries and showed they could be used to identify tumor suppressors. Ultimately our goal is to screen of complex pools of shRNA expressing retroviruses each marked with a bar code that allows the results of the screen to be read out by microarray hybridization. We demonstrated this could be accomplished in enrichment screens for shRNAs that caused cellular transformation and growth in soft agar. However, a key goal has been to identify shRNAs that debilitate or kill cancer cells. In order for this to be possible in complex pools, it is imperative that each vector knock down its target with high penetrance. We have successfully achieved this level of knockdown and can now see particular shRNA expressing viruses drop out of complex pools.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research