Ribozyme Targeting the Novel Fusion Junction of EGFRvIII in Breast Cancer

Abstract

EGFRvIII is a tumor specific, ligand-independent, constitutively active variant of the epidermal growth factor receptor. Its expression has been detected in gliomas and various other human malignancies. In order to evaluate the importance of EGFRvIII expression in human breast cancer, we examined the frequency of EGFRvIII protein expression immunohistochemically in paraffin embedded specimens from 109 patients with breast cancer. With a specific anti-EGFRvIII antibody, 67% (73 of 109) of primary breast carcinomas and 16% of DCIS (2/12) expressed EGFRvIII. No EGFRvIII expression was detected in normal breast tissue and benign tumors. We also observed 56% (413 of 564) in a breast cancer tissue microarray. These results confirm our pilot studies and suggested that expression of EGFRvIII may play a crucial role in breast cancer progression. To delineate the biological significance of EGFRvIII in human breast cancer, we expressed EGFRvIII in MCF-7 human breast cancer cells. Expression of EGFRvIII in MCF-7 produced a constitutively activated EGFRvIII receptor. These MCF-7/EGFRvIII transfectants exhibited approximately a three-fold increase in colony formation in 1% serum with no significant effect observed at higher percentages of serum. Collectively, these results provide the first evidence that EGFRvIII could play a pivotal role in human breast cancer progression.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2000
Accession Number
ADA385642

Entities

People

  • Careen Tang

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Alkanes
  • Antibodies
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Chemistry
  • Growth Factors
  • Laboratory Animals
  • Materials
  • Molecules
  • Neoplasms
  • Pilot Studies
  • Proteins
  • Recombinant Dna
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Biology and Genetics