Hypoxia as a Driving Force for Genetic Instability During Breast Tumorigenesis

Abstract

The overall hypothesis that drives this project is that persistent replication stress generates mutational events in breast epithelial cells that fuel breast cancer (BCa) progression. Our model predicts that a major source of replicative stress in BCa is hypoxia, which stalls active replication forks, and selects for cells that have bypassed this S-phase checkpoint due to mutations in the ATR-hchkl pathway. The specific aims of this project are: (1) to define the role of the ATR checkpoint pathway in hypoxia-induced cytostasis, and (2) to determine whether sensitivity to killing by certain anticancer agents. Hypoxia, Genetic Instability, Cell-Cycle Checkpoints, Cancer Chemotherapy

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2005
Accession Number
ADA457513

Entities

People

  • Robert T. Abraham

Organizations

  • Sanford Burnham Prebys Medical Discovery Institute

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Antineoplastic Agents
  • Biomedical Research
  • Breast Cancer
  • California
  • Cell Physiological Processes
  • Cells
  • Chemotherapy
  • Department Of Defense
  • Electronic Mail
  • Epithelial Cells
  • Information Operations
  • Instability
  • Maryland
  • Neoplasms

Fields of Study

  • Biology

Readers

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

Technology Areas

  • Biotechnology