Accession Number : ADA338870

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

Descriptive Note : Final rept. 15 May 94-14 May 97

Corporate Author : UTAH UNIV SALT LAKE CITY

Personal Author(s) : Worthylake, Becky

PDF Url : ADA338870

Report Date : JUN 1997

Pagination or Media Count : 17

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.

Descriptors :   *EPIDERMIS, *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *BREAST CANCER, EPITHELIUM, HUMANS, ENZYMES, TARGETING, MOLECULAR BIOLOGY, KINETICS, CELLS(BIOLOGY), RECEPTOR SITES(PHYSIOLOGY), CYTOLOGY.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE