Decreased Src tyrosine kinase activity inhibits malignant human ovarian cancer tumor growth in a nude mouse model
| Autor: | J R, Wiener, K, Nakano, R P, Kruzelock, C D, Bucana, R C, Bast, G E, Gallick |
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| Rok vydání: | 1999 |
| Předmět: |
Ovarian Neoplasms
Vascular Endothelial Growth Factor A Lymphokines Neovascularization Pathologic Vascular Endothelial Growth Factors Proto-Oncogene Proteins pp60(c-src) Gene Expression Mice Nude Endothelial Growth Factors Oligonucleotides Antisense Blotting Northern Transfection Immunohistochemistry Platelet Endothelial Cell Adhesion Molecule-1 Disease Models Animal Mice Tumor Cells Cultured Animals Humans Female RNA Messenger Cell Division Neoplasm Transplantation |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 5(8) |
| ISSN: | 1078-0432 |
| Popis: | The Src protein tyrosine kinase is overexpressed and activated in a number of human cancers, including some human ovarian cancers. To determine whether Src activity plays a role in ovarian tumor growth, stable derivatives of the SKOv-3 human ovarian cancer cell line that exhibited reduced Src tyrosine kinase activity were generated by transfection with an antisense c-src construct. Comparison of these cell lines with parental SKOv-3 cells and stable sense c-src vector-transfected control lines revealed no phenotypic alterations in anchorage-dependent proliferation, adherence, density saturation, or wound migration. However, reduction in Src activity was associated with altered cellular morphology, dramatically reduced anchorage-independent growth, and, when assessed for tumor development in a xenograft nude mouse model, diminished tumor growth. Furthermore, reduction of Src activity in the antisense c-src cell lines was associated with reduced vascular endothelial growth factor mRNA expression in vitro, and tumors derived from these cell lines displayed a phenotype indicative of abortive microvessel vascularization. These results strongly suggest that Src is involved in critical oncogenic pathways that modulate tumor growth from this ovarian cell line. Furthermore, this evidence suggests that as in other tumor systems, Src activity is required for vascular endothelial growth factor induction and angiogenic development. |
| Databáze: | OpenAIRE |
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