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Effects of gastrokine-2 expression on gastric cancer cell apoptosis by activation of extrinsic apoptotic pathways
Gastrokine-2 is a putative gastric cancer-specific tumor suppressor gene, the loss of which is known to be involved in the development and progression of gastric cancer, and restoration of gastrokine-2 expression inhibits growth of gastric cancer cells in vitro. However, the underlying mechanism of...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227429/ https://www.ncbi.nlm.nih.gov/pubmed/25270871 http://dx.doi.org/10.3892/mmr.2014.2603 |
Sumario: | Gastrokine-2 is a putative gastric cancer-specific tumor suppressor gene, the loss of which is known to be involved in the development and progression of gastric cancer, and restoration of gastrokine-2 expression inhibits growth of gastric cancer cells in vitro. However, the underlying mechanism of these effects requires elucidation. In the present study, expression patterns of gastrokine-2 protein were examined in gastric cancer tissues and cell lines. Expression of gastrokine-2 was restored in gastric cancer cells in order to assess its effect on cell viability, apoptosis and gene expression. A total of 76 gastric cancer tissues with corresponding normal mucosae samples, and two gastric cancer cell lines (SGC-7901 and AGS) were subjected to western blot analysis of gastrokine-2 expression. SGC-7901 cells were transiently transfected with gastrokine-2 cDNA and then treated with anti-CD95 and/or anti-Fas antibodies prior to analysis of cell viability, apoptosis and gene expression levels. Expression of gastrokine-2 protein was reduced or absent in gastric cancer tissues and gastric cancer cell lines. Following restoration of gastrokine-2 expression, the protein expression level of Fas was significantly increased, but no marked change was observed in the levels of bcl-2 and Bax proteins. Expression of gastrokine-2 protein reduced gastric cancer cell viability and induced apoptosis. Activity of caspase-3 and caspase-8 was increased, but caspase-9 activity remained unchanged in the SGC-7901 cells. Reduction or knockout of gastrokine-2 protein expression may contribute to gastric cancer development or progression, as the current study demonstrated that restoration of gastrokine-2 expression induces apoptosis of gastric cancer cells through the extrinsic apoptosis pathway. |
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