Oxidative Stress Increases the Blood Brain Barrier Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers

Abstract

BRCA1 is a multifunctional tumor suppressive protein. Knockout of WT BRCA1 in breast cancer cells resulted in an increase in cell proliferation, anchorage-independent growth, cell migration, invasion and a loss of p21/Waf1 and P27Kip1 expression. Further, in BRCA1 knocked-down cells, the expression of survivin was significantly up-regulated with a decrease in cellular sensitivity to paclitaxel. Cells that harbor endogenous mutant or defective BRCA1 (such as MDA-MB-436 and HCC1937) were highly proliferative and expressed a relatively low levels of p21/Waf1 and p27Kip1 and high level of survivin and were resistant to paclitaxel. Thus, mutated BRCA1 or loss of WT BRCA1 up-regulates the malignant cell behavior. However, it is still not clear how tumor cells expressing mutant BRCA1 have enhance tumorogenicity in vivo.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2013
Accession Number
ADA576308

Entities

People

  • Hava Avraham

Organizations

  • Beth Israel Deaconess Medical Center

Tags

DTIC Thesaurus Topics

  • Arteries
  • Biomedical Research
  • Blood-Brain Barrier
  • Breast Cancer
  • Cell Movement
  • Cells
  • Culture Techniques
  • Department Of Defense
  • Electronic Mail
  • Endothelial Cells
  • Intercellular Junctions
  • Migration
  • Neoplasms
  • Oxidative Stress

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Oncology (Cancer Research).