title: Differential susceptibility of gastric cancer cells to TRAIL-induced             apoptosis.
abstract: Understanding the molecular basis of the differential sensitivity of cancer             cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated             apoptosis is required to predict therapeutic outcomes and to improve the effectiveness             of TRAIL-based therapy. This study aimed to compare the responsiveness of gastric             cancer cells to TRAIL treatment and to investigate the molecular basis of the             differential TRAIL sensitivity of four gastric cancer cell lines. The TRAIL sensitivity             of the four cell lines was ranked in the following order: SNU-16 ≈ SNU-620 >             SNU-5 >> SNU-1. The level of Annexin V binding and the activation profile             of caspase-3, -8 and -9 corroborated the differential TRAIL susceptibility of             the cell lines. To determine the molecular basis of the differential sensitivity             to TRAIL, we examined the expression of signaling components involved in TRAIL-mediated             apoptosis. The mRNA level and surface expression of death receptor 4 (DR4) were             significantly decreased in the SNU-1 cells compared to the other cell lines. Bid             cleavage and X-linked inhibitor of apoptosis (XIAP) degradation were significantly             increased in the SNU-16 and SNU-620 cells compared to the SNU-5 and SNU-1 cells,             although Bid and XIAP were expressed at similar levels across the four cell lines.             The expression and degradation of FLICE-inhibitory protein (FLIP) upon TRAIL treatment             was independent of TRAIL sensitivity. In conclusion, the differential susceptibility             of the four gastric cancer cells to TRAIL may be ascribed to the differential             expression of DR4 and the proper augmentation of the death signal by the truncation             of Bid and degradation of XIAP.
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang,                     Kyonggi-do 431-060, Republic of Korea.
authors.forename: Nak-Mi
authors.initials: NM
authors.lastname: Song
authors.forename: Suyeon
authors.initials: S
authors.lastname: Jun
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Zang
authors.forename: Sung Gyun
authors.initials: SG
authors.lastname: Kim
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Park
authors.forename: Dongchul
authors.initials: D
authors.lastname: Kang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D006801:Humans; D020128:Inhibitory Concentration 50; D059748:Proteolysis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D013274:Stomach Neoplasms; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D020169:Caspases