Functional Geonic Analysis of Breast Cancer Cell Tumorigenicity Using a Noval Gene Silencing Resource
Abstract
We have identified approximately 30 genes that negatively impact the growth of Erb-B2 positive breast cancer 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. The PBP and NR1D1 genes are interesting because they give new insight into a pathway that can be exploited as a potential therapeutic target. Year 3 of funding resulted in finding that inhibition of PBP-PPAR?-NR1D1 does not affect ERBB2 signaling in breast cancer cells. That this pathway is overactive in her-2/neu breast cancer cells is likely due to the tight genetic linkage of Nr1D1 and her-2. We have also found that the PBP-PPAR?-NR1D1 pathway alters fat metabolism in breast cancer cells and have identified lipotoxicity as a likely mechanism for triggering apoptosis in the her-2/neu positive breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA477103
Entities
People
- Douglas S. Conklin
Organizations
- State University of New York at Albany