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

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-β1–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, α-catenin and, to a lesser extent, β-catenin. Changes in the expression of these proteins were associated with a reduction in complex formation among E-cadherin, β-catenin and α-catenin and between β-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. Int. J. Cancer 88:566–574, 2000. © 2000 Wiley-Liss, Inc.