BCL2L10 protein regulates apoptosis/proliferation through differential pathways in gastric cancer cells
| Autor: | Zi Wen Long, Jia-Wen Xu, Xi Xi Cao, Xiuping Liu, Tomoko Furuya, Jing Da Xu, Qing-Quan Li, Kohsuke Sasaki, Xiao-Li Liu, Zu-De Xu |
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| Rok vydání: | 2010 |
| Předmět: |
Programmed cell death
Transplantation Heterologous Bisulfite sequencing Mice Nude Apoptosis Biology Pathology and Forensic Medicine Mice Phosphatidylinositol 3-Kinases Stomach Neoplasms Tumor Cells Cultured Carcinoma medicine Animals Humans RNA Small Interfering Promoter Regions Genetic Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction Cell growth Cancer DNA Methylation medicine.disease Mitochondria Proto-Oncogene Proteins c-bcl-2 Gene Knockdown Techniques DNA methylation Cancer cell Cancer research CpG Islands Female Proto-Oncogene Proteins c-akt Neoplasm Transplantation Signal Transduction |
| Zdroj: | The Journal of Pathology. 223:400-409 |
| ISSN: | 0022-3417 |
| Popis: | The reason for and consequences of BCL2L10 down-regulation in gastric carcinoma are poorly understood. Our aim was to investigate the function of the protein BCL2L10 in gastric carcinoma. We investigated BCL2L10 expression using quantitative real-time PCR and immunoblotting. The methylation status of the BCL2L10 gene promoter was examined by bisulphite sequencing in fresh gastric normal and carcinoma tissues. We studied apoptosis and proliferation regulation in gastric cancer cell lines using flow cytometry, fluorescence staining, murine xenografting and immunoblotting. Pathway inhibitors were applied to confirm the major pathways involved in apoptosis or proliferation regulation. We observed significant correlations between lower BCL2L10 expression and CpG island hypermethylation of the BCL2L10 gene promoter in gastric carcinoma, apoptosis induced by over-expressed BCL2L10 through mitochondrial pathways, and proliferation accelerated by BCL2L10 siRNA via the PI3K-Akt signalling pathway in gastric cancer cell lines. The pro-apoptotic effect of BCL2L10 and growth promotion by BCL2L10 siRNA in gastric cancer cells suggest that it may be a tumour suppressor. |
| Databáze: | OpenAIRE |
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