Functional Geno,ic Analysis of Breast Cancer Cell Tumorigenicity Using a Noval Gene Silencing Resource
Annual rept. 31 Mar 2005-30 Mar 2006
STATE UNIV OF NEW YORK AT ALBANY RESEARCH FOUNDATION
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The year 1 aims were primarily concerned with collecting shRNA constructs so that a small number that have inhibitory effects on breast cancer progression in vivo models could be identified. We have collated a set of encoded hairpins targeting genes overexpressed in ErbB-2 positive breast tumors. We have also spent considerable effort testing the compatibility of several assays for cellular correlates of tumorigenicity with high throughput gene transfer. To date we have retrieved 65 shRNA constructs targeting 51 of the genes overexpressed ErbB2-positive breast cancer cells and tested them for effects on cell proliferation in a screen in BT474 cells. Year 2 of funding resulted in tests of the specificity of the shRNAs negative impact on the growth of Erb-B2 positive breast cancer cells. Effects of these shRNAs on normal cells and other breast cancer cell lines identified approximately 20 shRNAs that specifically inhibit Erb-B2 positive breast cancer cells target genes. Several of these gene targets are known to be important to a variety of cancers. Two novel genes are interesting because they give new insight into a pathway that can be exploited as a potential therapeutic target.
- Anatomy and Physiology
- Medicine and Medical Research