Tumor necrosis factor-related apoptosis-inducing ligand and its receptor expression and the pathway of apoptosis in human pancreatic cancer

Methodology: 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-(4,5dimethylthiazol-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. Conclusion: 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.