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

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2001
Accession Number
ADA394717

Entities

People

  • Adrian P. Smith
  • John A. Lee
  • Steven I. Reed

Organizations

  • Scripps Research

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Carcinoma
  • Cells
  • Chromosomes
  • Connective Tissue
  • Epithelium
  • Genes
  • Genetics
  • Genomic Instability
  • Genotypes
  • Instability
  • Kinetics
  • Mammary Glands
  • Medical Personnel
  • Neoplasms
  • Tissues

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Oncology (Cancer Research).