Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells

Int J Cancer. 2000 Nov 15;88(4):566-74. doi: 10.1002/1097-0215(20001115)88:4<566::aid-ijc8>3.0.co;2-d.

Abstract

Over-expression of epidermal growth factor receptor (EGFR) in ovarian cancer has been well documented. Human NIH:OVCAR-8 ovarian carcinoma cells were transfected with an expression vector containing the anti-sense orientation of truncated human EGFR cDNA. EGFR anti-sense over-expression resulted in decreased EGFR protein and mRNA expression, cell proliferation and tumor formation in nude mice. In accordance with the reduced levels of EGFR in EGFR anti-sense-expressing cells, tyrosine phosphorylation of EGFR was decreased compared to untransfected parental cells treated with EGF. In EGFR anti-sense-transfected cells, expression of erbB-3, but not erbB-2, was increased. In addition, basal and heregulin-beta 1-stimulated tyrosine phosphorylation of erbB-3 was higher in EGFR anti-sense vector-transfected cells. A morphological alteration in EGFR anti-sense gene-expressing cells was correlated with a decrease in the expression of E-cadherin, alpha-catenin and, to a lesser extent, beta-catenin. Changes in the expression of these proteins were associated with a reduction in complex formation among E-cadherin, beta-catenin and alpha-catenin and between beta-catenin and EGFR in EGFR anti-sense-expressing cells compared to sense-transfected control cells. These results demonstrate that EGFR expression in ovarian carcinoma cells regulates expression of cell adhesion proteins that may enhance cell growth and invasiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cell Adhesion / genetics*
  • Cell Division / genetics
  • Cytoskeletal Proteins / genetics
  • DNA, Antisense / genetics*
  • ErbB Receptors / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / physiopathology
  • Receptor, ErbB-3 / analysis
  • Receptor, ErbB-3 / genetics
  • Trans-Activators*
  • Transcription, Genetic / genetics
  • Transfection
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • alpha Catenin
  • beta Catenin

Substances

  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cadherins
  • Ctnna1 protein, mouse
  • Cytoskeletal Proteins
  • DNA, Antisense
  • Trans-Activators
  • alpha Catenin
  • beta Catenin
  • ErbB Receptors
  • Receptor, ErbB-3