Tumor necrosis factor-related apoptosis-inducing ligand and its receptor expression and the pathway of apoptosis in human pancreatic cancer.
METHODS
The authors performed the reverse transcription-polymerase chain reaction (RT-PCR) in 17 cases of pancreatic ductal cell carcinoma (PDC) and five cases of normal pancreatic tissues to determine the expression of tumor necrosis factor -related apoptosis-inducing factor (TRAIL) and its five receptors in PDC.


RESULTS
The expression of TRAIL and its receptors other than osteoprotegerin was found frequently in both PDC and normal tissues. whereas the expression of osteoprotegerin was detected only in PDC. The authors detected cancer cell death by TRAIL, ranging from 37% to 77% in all the PDC cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Hochest staining revealed that cell death was caused by apoptosis. Caspase-8 and caspase-3 and poly (ADP-ribose) polymerase cleavage was activated within 2 hours after stimulation with 200 ng/mL TRAIL.


CONCLUSIONS
These findings suggest a relation between osteoprotegerin expression and the biologic aggressiveness of PDC and the involvement of caspase-8 and caspase-3 activation in the TRAIL-mediated apoptosis pathway in PDC.
Satoh
K
K
Department of Gastroenterology, Tohoku University Graduate School of Medicine, Aobaku, Sendai, Japan. ksatoh@int3.med.tohoku.ac.jp
Kaneko
K
K
Hirota
M
M
Masamune
A
A
Satoh
A
A
Shimosegawa
T
T
D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000494:pharmacology; D053244:Osteoprotegerin; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C506030:TNFRSF11B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases