title: BCL2L10 protein regulates apoptosis/proliferation through differential pathways in gastric cancer cells.
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.
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University,Shanghai 200032, People's Republic of China.
authors.forename: Jing Da
authors.initials: JD
authors.lastname: Xu
authors.forename: Xi Xi
authors.initials: XX
authors.lastname: Cao
authors.forename: Zi Wen
authors.initials: ZW
authors.lastname: Long
authors.forename: Xiu Ping
authors.initials: XP
authors.lastname: Liu
authors.forename: Tomoko
authors.initials: T
authors.lastname: Furuya
authors.forename: Jia Wen
authors.initials: JW
authors.lastname: Xu
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Liu
authors.forename: Zu
authors.initials: Z
authors.lastname: De Xu
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Qing Quan
authors.initials: QQ
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D049109:Cell Proliferation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000502:physiology; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: C117144:BCL2-like 10 protein; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt