EGFR-Dependent Regulation of Matrix-Independent Epithelial Cell Survival

Abstract

Background: Signaling through the epidermal growth factor receptor (EGFR) has been implicated in both effective wound healing and epithelial neoplasia. We have identified a novel function of the EGFR in support of epithelial cell survival, particularly in conditions of anchorage-independence. Furthermore, we have implicated MEK/MAPK signaling in this process. Objective/hypothesis: Define molecular mechanisms and pathways by which EGFR activation supports epithelial cell survival. Two specific aims focus on: 1) post translational modification of relevant Bcl-2 family members by EGFR activation through MAPK-dependent mechanisms and, 2) STAT3 activation by deregulated EGFR signaling as observed in epithelial cancer. Progress: During the last funding period we have focused on modification of Bcl-2 family members during suspension culture. Specifically, we have characterized the pro-apoptotic Bcl-2 family member BIM to be upregnlated during suspension culture and, potentially, phosphorylated by EGFR activation. These results are very encouraging and will be pursued further. The studies proposed under Specific Aim 2 have been completed and have been accepted for publication.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2004
Accession Number
ADA426140

Entities

People

  • Ulrich Rodeck

Organizations

  • Thomas Jefferson University

Tags

DTIC Thesaurus Topics

  • Biological Sciences
  • Biology
  • Biotechnology
  • Cancer
  • Carcinoma
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Epithelial Cells
  • Growth Factors
  • Neoplasms
  • Proteins
  • Regulations
  • Survival
  • Tissue Extracts
  • Tyrosine

Fields of Study

  • Biology
  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Cellular and Molecular Pathways of Apoptosis.