Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells
| Autor: | O, Alper, M L, De Santis, K, Stromberg, N F, Hacker, Y S, Cho-Chung, D S, Salomon |
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| Rok vydání: | 2000 |
| Předmět: |
Ovarian Neoplasms
Receptor ErbB-3 Transcription Genetic Genetic Vectors Mice Nude Cadherins Transfection Xenograft Model Antitumor Assays DNA Antisense ErbB Receptors Gene Expression Regulation Neoplastic Cytoskeletal Proteins Mice Cell Adhesion Trans-Activators Tumor Cells Cultured Animals Humans Female Cell Division alpha Catenin beta Catenin |
| Zdroj: | International journal of cancer. 88(4) |
| ISSN: | 0020-7136 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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