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-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.
Alper
O
O
Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
De Santis
M L
ML
Stromberg
K
K
Hacker
N F
NF
Cho-Chung
Y S
YS
Salomon
D S
DS
D000818:Animals; D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D020893:Receptor, ErbB-3 / Q000032:analysis / Q000235:genetics; D015534:Trans-Activators; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D016373:DNA, Antisense; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D066246:ErbB Receptors; D020893:Receptor, ErbB-3