Zinc Finger Transcription Factors as Novel Switches to Modulate Metastatic Progression of Breast Tumors
Annual rept. 16 Apr 2006-17 Apr 2007
NORTH CAROLINA UNIV AT CHAPEL HILL
Pagination or Media Count:
The transcriptional programs cooperatively required for the malignant progression of breast tumors are largely unknown. In this project we propose the isolation of Artificial Transcription Factors TFs for the discovery of gene panels, which cooperate during the generation of metastatic behavior. An ATF is made by linkage of a DNA-binding domain DBDwith a transcriptional effect or domain, which mediates activation or repression of endogenous genes. ATFs are typically made of arrays of Cys2-His2 zinc finger ZF domains. The objective of this proposal is to apply large ATF libraries to identify and regulate genes that cooperate during the process induction of breast cancer cell invasion and progression. We have delivered ATF libraries into non-invasive breast cancer cell lines. We have selected ATFs able to induce or enhance breast cell invasion. The ATF-selections were performed in vitro using materiel invasion assays Boyden chambers. In the future, ATFs modulating cell invasion will be profiled using DNA microarrays to determine genes differentially regulated by the ATF that are responsible for the phenotype change.
- Anatomy and Physiology
- Medicine and Medical Research