Study on the anti-invasion effect of SEPT7 gene for U251MG glioma cell in vitro / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
;
(6): 262-267, 2008.
Artículo
en Chino
| WPRIM
| ID: wpr-229777
ABSTRACT
<p><b>OBJECTIVE</b>To study the anti-invasion effect of SEPT7 gene on U251MG glioma cells and its possible molecular mechanism.</p><p><b>METHODS</b>Recombinant adenovirus vector carrying SEPT7 gene (rAd5-SEPT7) was transduced to human glioma cell line U251MG, and empty adenovirus vector was used as control. Tumor invasion was examined by Transwell method and 3 D-Matrigel assay, and tumor cell migration by wound-healing method and 2 D-Matrigel assay. Three major molecular events associated with cell motility and migration, including changes of expression in MMP2, MMP9, MT1-MMP, TIMP1 and TIMP2, the alteration of integrin alpha(v)beta(3) expression, and the structural change of cytoskeleton protein, tubulin-alpha, in U251 cells transduced with rAd5-SEPT7 were studied by Western blotting, immunofluorescence and laser scanning confocal microscope, respectively.</p><p><b>RESULTS</b>The invasive and migratory capabilities of cells transduced with rAd5-SEPT7 were inhibited. The expression of extracellular matrix metalloproteinases MMP-2, MMP-9, MT1-MMP and integrin alpha(v)beta(3) was significantly decreased, while the expression of matrix metalloproteinase inhibitor TIMP1, TIMP2 was upregulated. Intracellular cytoskeleton protein-tubulin-alpha in U251 cells exhibited prominent morphological changes which including the appearance of distortion and aggregation resulting from redistribution of tubulin-alpha, and this feature of alteration was similar to the tubulin-alpha structure in normal non-tumor cells.</p><p><b>CONCLUSION</b>SEPT7 gene can inhibit the invasion and migration ability of U251 glioma cells. Its molecular mechanism may include that SEPT7 gene reverses the imbalanced state of MMPs/TIMPs, downregulates the expression of integrin alpha(v)beta(3) and alters the structure of tubulin-alpha of U251MG glioma cells. It is suggested that SEPT7 gene could be a good candidate for gene therapy of gliomas.</p>
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Patología
/
Fisiología
/
Movimiento Celular
/
Adenoviridae
/
Western Blotting
/
Microscopía Confocal
/
Proteínas de Ciclo Celular
/
Inhibidor Tisular de Metaloproteinasa-1
/
Inhibidor Tisular de Metaloproteinasa-2
/
Metaloproteinasa 2 de la Matriz
Límite:
Humanos
Idioma:
Chino
Revista:
Chinese Journal of Medical Genetics
Año:
2008
Tipo del documento:
Artículo
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