Functional Genomic Analysis of Breast Cancer Cell Tumorigenicity Using a Novel Gene Silencing Resource
Annual rept. 31 Mar 2004-30 Mar 2005
STATE UNIV OF NEW YORK AT ALBANY
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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. In the past year, we have a 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 tumorigenicty 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. Somewhat surprisingly, almost 35 of the hairpins used in the screening cause similar or greater reduction of cell proliferation than ErbB-2 shRNA controls. Although several of the genes whose decreased expression compromises proliferation rate have been shown to play a role in tumor cell growth, it is clear that these constructs must now be tested for effects on normal cells, i.e. human mammary epithelial cells HMECs, to assess whether these represent pathways that are required specifically for tumor cell proliferation.
- Medicine and Medical Research