Q Liao1, H Friess, J Kleeff, M W Büchler. 1. Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Abstract
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.
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 humanpancreatic 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.
Authors: Guido M Sclabas; Shuichi Fujioka; Christian Schmidt; Zhen Fan; Douglas B Evans; Paul J Chiao Journal: J Gastrointest Surg Date: 2003-01 Impact factor: 3.452
Authors: Tom M Ganten; Jaromir Sykora; Ronald Koschny; Emanuela Batke; Sebastian Aulmann; Ulrich Mansmann; Wolfgang Stremmel; Hans-Peter Sinn; Henning Walczak Journal: J Mol Med (Berl) Date: 2009-08-13 Impact factor: 4.599