Role of ERBB-2 in Breast Cancer Progression.

Abstract

Overexpression of growth factors and growth factor receptors is frequently associated with loss of estrogen receptor (ER) in human breast cancer, leading to the hypothesis that constitutive expression of these proteins might decrease dependence on estrogen. We have previously investigated the role of one putative growth factor receptor, c-erbE-2, in loss of hormone dependence by transfection of the c-erbB-2 cDNA into ER+ human breast cancer cells. We found that the size of the tumors formed correlated with the degree of tyrosine phosphorylation of the transfected protein. We hypothesized that an increase in tyrosine phosphor- ylation might increase the tumorigenicity of the cells. We therefore transfected ER+ MCF-7 cells with wild type and constitutively active mutant c-erbB-2 cDNAs. We found that we were able to stably overexpress the wild type protein only in the absence of estrogen, and that we were unable to stably overexpress the mutant protein under any growth conditions. Subsequent transfection of the mutant c-erbB-2 using a tetracycline-regulated gene expression system suggested that constitutive expression of this protein might induce apoptosis in breast cancer cells. These results suggest an important role for c-erbB-2 in regulation of the growth of breast cancer cells.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 1995
Accession Number
ADA302257

Entities

People

  • Francis G. Kern

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Anti-Bacterial Agents
  • Apoptosis
  • Breast Cancer
  • Cell Line
  • Cells
  • Chemistry
  • Estrogens
  • Gene Expression
  • Growth Factors
  • Mutant Proteins
  • Neoplasms
  • Peptide Growth Factors
  • Proteins
  • Transfection
  • Tumor Cell Line
  • Tyrosine

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.