Breast Tumor Kinetics in Mice Overexpressing Cyclin E and Heterozygous for Tumor Suppressor p53 or Rb
Annual summary rept. 1 May 2000-30 Apr 2001
SCRIPPS RESEARCH INST LA JOLLA CA
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The purpose of this project is to test whether deregulated cyclin E in the mammary epithelia predisposes to chromosomal instability and hence mammary tumorigenesis. To test this hypothesis based on in vitro work we have crossed transgenic mice expressing either wild-type human cyclin E or a hyperstable mutant T380A with mice heterozygous at either the p53 or Rb loci. If genomic instability is induced by deregulated expression in the mammary epithelia, we anticipate an increased penetrance and decreased latency of tumorigenesis. In the first 12 months we have successfully established the 9 genotypes of mice necessary for this project and have established protocols for histopathological and karyotype analysis. Pathological findings observed to date are all in keeping with published genotype-specific tumor types with the exception of those in the newly established strains, the significance of which will not be established until greater numbers have been studied. Although this project is in its early stages, all practical objectives to achieve its completion have been met. I have an excellent working relationship with two experienced pathologists both veterinary and medical to maximise interpretation of the results.
- Medicine and Medical Research