Differential expression of TRAIL-R3 and TRAIL-R4 in human pancreatic cancer

BACKGROUND: Pancreatic cancer is one of the most aggressive cancers, in part due to its insensitivity to most treatment modalities. This resistance towards cytotoxic therapy is thought to be caused--at least in part--by a general resistance of pancreatic cancer cells towards apoptosis. TRAIL-R3 and TRAIL-R4, which belong to the TRAIL receptor family, can inhibit TRAIL-induced apoptosis. PATIENTS AND METHODS: Seven normal pancreatic tissues and 7 pancreatic cancer tissues were analyzed using Northern blotting, Western blotting and immunohistochemistry. RESULTS: TRAIL-R3 mRNA and protein expression were generally weak in pancreatic cancers and normal pancreatic tissues. In contrast, TRAIL-R4 mRNA and protein were expressed at moderate to high levels in human pancreatic cancer tissues, but demonstrated weak to negative expression in the normal pancreas. CONCLUSION: TRAIL-R4 but not TRAIL-R3 levels were significantly different in pancreatic cancer in comparison to the normal pancreas. These findings give new insight into the resistance mechanisms of pancreatic cancer towards TRAIL-mediated apoptosis.