Study the Pathogenic Role of ErbB-3, ErbB-4 and their Ligand Heregulin in Human Breast Cancer Cell

Abstract

Among the growth factor receptors, members of the class I receptor tyrosine kinase family (ErbB) is most frequently implicated in human breast cancers. To delineate the biological function of ErbB-4 receptors in breast cancer, we employed a hammerhead ribozyme strategy to achieve down-regulation of ErbB-4 receptors in various breast cancer cell lines. We observed that down-regulation of ErbB-4 in estrogen receptor positive (ER+) cell lines (MCF-7 and T47D) resulted in a reduction of tumorigenicity both in vitro and in vivo. However, over time completely down-regulation of ErbB-4 in ER+ cell lines acquired the ability to up-regulate EGFR or ErbB-2 and progressed to a hormone-independent phenotype. These results mimics the clinical observation. Overexpression of EGFR and ErbB-2 is inversely correlated with ER. The expression of ErbB-4 was correlated with ER+ and PgR+ primary breast tumors by immunohistochemistry. These results suggested that ErbB-4 plays different roles in breast cancer progression.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Jul 01, 1999
Accession Number
ADB251995

Entities

People

  • Careen Tang

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Gene Expression
  • Growth Factors
  • Health Services
  • Medical Personnel
  • Neoplasms
  • Peptide Growth Factors
  • Proteins

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.