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BCL2L10 protein regulates apoptosis/proliferation through differential pathways in gastric cancer cells
- Source :
- The Journal of Pathology. 223:400-409
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 00223417
- Volume :
- 223
- Database :
- OpenAIRE
- Journal :
- The Journal of Pathology
- Accession number :
- edsair.doi.dedup.....1b95313215325cdee918729ca324879c