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.


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.


CONCLUSIONS
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.
Liao
Q
Q
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Friess
H
H
Kleeff
J
J
Büchler
M W
MW
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D005260:Female; D058851:GPI-Linked Proteins; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053319:Tumor Necrosis Factor Decoy Receptors
D058851:GPI-Linked Proteins; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C105190:TNFRSF10A protein, human; C108661:TNFRSF10C protein, human; D053319:Tumor Necrosis Factor Decoy Receptors