Role of erbB-2 and erbB-3 in the Activation of Phosphatidylinositol 3-Kinase

Abstract

We sought to assess the importance of cooperative interaction between p185erbB-2 and erbB-3 in the growth factor-independent proliferation and neoplastic transformation of breast carcinoma cells with c-erbB-2 gene amplification. We have now successfully produced cell populations derived from MCF-10A normal mammary epithelial cells that overexpress c-erbB-2 at very high levels comparable to that seen in breast carcinoma+ cells with c-erbB-2 gene amplification. While the original clones of MCF-10AerbB-2 cells overexpress c-erbB-2 at only moderate levels and are not tumorigenic in nude mice, MCF-19AerbB-2shH cells selected for high-level c-erbB-2 overexpression with growth factor,independence in culture show a high level of constitutive PI 3-kinase activity and a highly transformed phenotype both in culture and in vivo. In addition, key observations were made during the course of these studies which provide important information concerning the survival and growth of cells, in the absence of growth factors that occurs as a function of the level of c-erbB-2 gene overexpression.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Jun 01, 1998
Accession Number
ADA353275

Entities

People

  • Stephen P. Ethier

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Amplification
  • Apoptosis
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Epithelial Cells
  • Fibroblasts
  • Gene Expression
  • Gene Therapy
  • Genes
  • Genetics
  • Growth Factors
  • Neoplasms
  • Proteins
  • Virotherapy

Fields of Study

  • Medicine

Readers

  • Molecular Biology and Genetics