The Effects of Signaling Through the EGF Receptor System Upon Regulation of Growth in Human Mammary Epithelial Cells

Abstract

Previous reports showed that transactivation of the human epidermal growth factor receptor 2 (HER2) by epidermal growth factor (EGF) leads to the downregulation of HER2. This report presents evidence that overexpression of HER2 nearly abolished its downregulation. Unexpectedly, downregulation of the epidermal growth factor receptor (EGFR) was also inhibited by overexpression of HER2. This suggests that the EGFR and HER2 share a trafficking component which becomes limiting when HER2 is overexpressed. There are two trafficking steps which kinetic analyses predict to be regulated by a saturable component: internalization and lysosomal targeting. We show that the internalization rate of the EGFR is independent of the level of HER2 expression. Thus, we speculate that the molecule responsible for lysosomal targeting is shared between EGFR and HER2. Further, this implies that overexpression of one of the EGFR family members can cause misregulation of the receptors expressed at normal levels.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 1997
Accession Number
ADA338870

Entities

People

  • Becky Worthylake

Organizations

  • University of Utah

Tags

DTIC Thesaurus Topics

  • Antibodies
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cells
  • Chemical Compounds
  • Epithelial Cells
  • Growth Factors
  • Laboratory Animals
  • Mammary Glands
  • Materials
  • Molecules
  • Neoplasms
  • Proteins
  • Recombinant Dna
  • Regulations
  • Targeting

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and Cellular Biochemistry