Impact of Disrupted BRCA2 Protein-Protein Interactions on DNA Repair and Tumorigenesis

Abstract

In this report, we have investigated the effects of overexpression of active Ras within the mammary epithelium. Using the tetracycline-inducible system, we have generated a line of mice which, when also bearing rtTA transgene expressed under control of the MMTV LTR, inducibly express active H-Ras in the mammary epithelium in response to the drug doxycycline. We have also shown that pathways downstream of Ras are activated, such as the Raf/MEK/MAPK pathway. We have shown that the mammary epithelium undergoes an increase in proliferation in response to Ras, but undergoes a proliferative arrest and inhibition of ductal elongation in chronically induced glands. This arrest occurs in the absence of increased apoptosis. Removal of doxycycline abrogates the growth arrest and restores a normal gland within 60 days. Finally, the pl9/p53/p2l pathway is activated in response to Ras.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2003
Accession Number
ADA425156

Entities

People

  • Christopher J. Sarkisian

Organizations

  • University of Pennsylvania

Tags

DTIC Thesaurus Topics

  • Albumins
  • Amino Acids
  • Anti-Bacterial Agents
  • Apoptosis
  • Biomedical Research
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Confocal Microscopy
  • Epithelium
  • Molecular Biology
  • Programmed Cell Death
  • Protein-Protein Interactions
  • Proteins
  • Stem Cells

Fields of Study

  • Biology
  • Medicine

Readers

  • Molecular Biology and Genetics

Technology Areas

  • Biotechnology