Molecular Mechanisms of Breast Cancer Metastasis

Abstract

The five-year survival rate for individuals with a primary breast tumor is 97%. In contrast, the five-year survival rate of individuals with breast cancer metastasis is 23%. Clearly, understanding the molecular mechanisms of metastasis are essential for the prediction and prevention of metastatic disease. Studies of the chromatin protein Heterochromatin Protein 1-alpha (HP1(Hs alpha)) will provide insights on the molecular changes that accompany breast cancer metastasis. HP1(HS alpha) is down-regulated in highly invasive/metastatic breast cancer cells compared with poorly invasive/non-metastatic breast cancer cells. This down-regulation is also observed in metastatic patient tissues. We have determined that transcriptional down-regulation of HP1(Hs alpha) in highly invasive/metastatic breast cancer cells occurs through an E-box element in the promoter region. To determine how levels of HP1(Hs alpha) regulate invasive properties we have expressed HP1(HS alpha) in highly invasive/metastatic breast cancer cells and knocked down levels of HP1(HS alpha) in poorly invasive/metastatic breast cancer cell lines. Our results demonstrate that addition of HP1(Hs alpha) into highly invasive cells reduces their invasive potential. Furthermore, HP1(HS alpha) dimerization is required for this reduction. Subsequent studies will be aimed at changes in gene expression that correlate with altered invasion.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA426421

Entities

People

  • Lori Wallrath

Organizations

  • University of Iowa

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Animal Structures
  • Birds
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Chromosome Structures
  • Chromosomes
  • Fungi
  • Gene Expression
  • Genetic Structures
  • Genetics
  • Metastasis
  • Neoplasms
  • Proteins
  • Tumor Cell Line

Readers

  • Battery Technology and Engineering
  • Molecular Biology and Genetics