Tissue Specific Chromosome Deletions: An In Vivo Genetic Screen for Tumor Suppressor Genes in the Mammary Glands

Abstract

Breast cancer is a genetic disease involving both gain and loss of function mutations in many different genes. It is important to define which genes are significant mutational targets in sporadic breast tumors so that treatments can be directed based on the knowledge of the genetic changes in the tumor. This proposal is focused on identifying tumor suppressor genes which are mutated in sporadic breast cancer. We proposed to identify these tumor suppressor genes by a novel genetic screen in vivo. This genetic screen involves the adaptation of our chromosome engineering technology to delete specific chromosomal regions in mouse mammary epithelial cells in vivo. We planned to use tissue specific expression of Cre in mammary epithelial cells to induce these deletion events in vivo. When combined with insertional mutagenesis this technology has the power to identify tumor suppressor genes mutated in breast cancer. In the first year of this proposal we have constructed several "pre-deletion" chromosomes, transmitted them into the germ line and tested recombination event in vivo. We have also evidence of tissue specific recombination in heart muscle. We have also generated a MMTV-Cre transgene in the hprt locus which is also in the mouse germ line.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
May 01, 1999
Accession Number
ADA381229

Entities

People

  • Allan Bradley

Organizations

  • Baylor College of Medicine

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chromosome Aberrations
  • Chromosome Structures
  • Chromosomes
  • Culture Techniques
  • Diseases And Disorders
  • Engineering
  • Epithelial Cells
  • Genes
  • Genetic Structures
  • Genetics
  • Mammary Glands
  • Neoplasms
  • Stem Cells

Fields of Study

  • Biology
  • Medicine

Readers

  • Molecular Biology and Genetics
  • Molecular Genetics

Technology Areas

  • Biotechnology