This research is designed to test the hypothesis that aneuploidy in some breast tumors is caused by centrosome abnormalities which are induced by alteration in p53 function. Specific mutations in p53 that are associated with breast cancer, aneuploidy, and centrosome abnormalities have been identified during the course of this project. We have shown that p53 mutations correlate with an increase in microtubule nucleating capacity however no such correlation is indicated with either centrosome size or centrosome number. To test whether or not a specific p53 mutation affects centrosome function, thus leading to chromosomal instability, attempts are being made to transfect normal mammary breast cells to over-express selected mutants of p53. Once transfected the cells will be monitored for changes in ploidy and centrosome structure and function. Due to the poor transfection efficiency using standard plasmid-based transfections with a number of different lipid transfection reagents. we have recently begun to construct adenoviral vectors for our mutant p53 studies. The high efficiency of transduction with these adenoviral vectors will allow us to perform our planned studies.
Annual summary rept. 1 Jun 2000-31 May 2001
--Original contains color plates: All DTIC reproductions will be in black and white.