title: Bcl-w is expressed in a majority of infiltrative gastric adenocarcinomas and suppresses the cancer cell death by blocking stress-activated protein kinase/c-Jun NH2-terminal kinase activation.
abstract: To determine a cellular factor supporting the survival of gastric cancer cells, a comparative study was performed using two human adenocarcinoma cell lines, SNU-16 and SNU-620. The latter cells were significantly less susceptible to various lethal stimuli including anti-Fas, H(2)O(2), etoposide, and serum withdrawal than the former. These stimuli were found to kill the SNU-16 cells by activating stress-activated protein kinase (SAPK)/c-Jun NH(2)-terminal kinase (JNK), whereas SAPK/JNK activation was not efficiently induced in the SNU-620 cells. Western blot analysis revealed that Bcl-w, but not the other tested members of the Bcl-2 family, was expressed in the SNU-620 cells to levels higher than that observed in SNU-16 cells. An elevation of the Bcl-w levels in the SNU-16 cells by its stable transfection attenuated both the SAPK/JNK activation and the cell death induced by all of the tested stimuli. These results suggest that the susceptibility of gastric cancer cells to death stimuli is determined, at least in part, by the levels of Bcl-w that suppress the cell death by blocking SAPK/JNK activation. To examine whether Bcl-w was expressed in patients, tumor specimens were obtained from 50 consecutive advanced gastric adenocarcinoma cases. An immunohistochemical analysis showed that Bcl-w was expressed in cancer cells but not in the neighboring normal mucosa of the 23 cases (46%). Interestingly, Bcl-w expression was associated significantly with certain histopathological characteristics of the cancer, notably with the infiltrative morphotypes (P < 0.001). Therefore, Bcl-w appears to be important for gastric cancer cell survival, particularly in infiltrative tumors.
authors.affiliation: Laboratory of Experimental Pathology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Seung-Sook
authors.initials: SS
authors.lastname: Lee
authors.forename: Sun Joo
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Um
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D011506:Proteins; D019014:fas Receptor; D005047:Etoposide; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases