Breast Tumor Kinetics in Mice Overexpressing Cyclin E and Heterozygous for Tumor Suppressor p53 or Rb

摘要

The purpose of this project was to test whether deregulated cyclin E in the mammary epithelia predisposes to chromosomal instability and hence tumorigenesis. To test this hypothesis, based on in vitro work (Spruck et al. 1999), we generated 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 were induced by deregulated expression in the mammary epithelia, we anticipated an increased penetrance and decreased latency of tumorigenesis. Neither heterozygosity of p53 or Rb predisposes to mammary tumorigenesis in mice (Jacks et al. 1992; Jacks et al. 1994; Harvey et al. 1995) except in the BALB/c background (Kuperwasser et al. 2000). The evaluation of this model has involved the integration of molecular and pathological analysis.