p63 in Development and Maintenance of the Prostate Epithelium
Final rept. 8 Feb 2006-7 Feb 2010
BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
Pagination or Media Count:
The purpose of this project is to define the role of p63 in the development and maintenance of the prostate epithelium by utilizing both in vivo and in vitro models. In the first two years of work, we have constructed the targeting vector for the generation of the p63-Cre-ERT2 knock-in mice. The p63-Cre-ERT2 vector has been electroporated in the ES cells. p63-Cre-ERT2 ES clones with successful targeting events have been obtained and injected in host blastocysts, resulting in the production of 5 high percentage p63-Cre-ERT2 chimeras, which are currently being bred. To date, two F1 p63-Cre-ERT2 knock-in pups have been generated. We have also continued to work on the identification of the molecular mechanisms through which p63 regulates development of the prostate epithelium. Specifically, the use of siRNA against p63 has been optimized in various cell lines and, most importantly, p63 shRNA inducible cell lines including iPrEC have been generated. Our results show that downregulation of p63 in iPrEC cells consistently causes a decrease in cell viability due to induction of apoptosis. Moreover, our data demonstrates that p63 modulates AKT and MAPK activation in iPrEC cells.
- Anatomy and Physiology
- Medicine and Medical Research