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 cha in reaction (RT-PCR) in 17 cases of pancreatic ductal cell carcinoma (PDQ a nd five cases of normal pancreatic tissues to determine the expression of t umor necrosis factor -related apoptosis-inducing factor (TRAIL) and its fiv e receptors in PDC. Results: The expression of TRAIL and its receptors other than osteoproteger in was found frequently in both PDC and normal tissues, whereas the express ion of osteoprotegerin was detected only in PDC. The authors detected cance r 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 wit hin 2 hours after stimulation with 200 ng/mL TRAIL. Conclusion: These findings suggest a relation between osteoprotegerin expre ssion and the biologic aggressiveness of PDC and the involvement of caspase -8 and caspase-3 activation in the TRAIL-mediated apoptosis pathway in PDC.