High TRAIL death receptor 4 and decoy receptor 2 expression correlates with significant cell death in pancreatic ductal adenocarcinoma patients.
OBJECTIVE
The importance of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor expression in pancreatic carcinoma development is not known. To reveal the putative connection of TRAIL and TRAIL receptor expression profile to this process, we analyzed and compared the expression profile of TRAIL and its receptors in pancreatic tissues of both noncancer patients and patients with pancreatic ductal adenocarcinoma (PDAC).


METHODS
Thirty-one noncancer patients and 34 PDAC patients were included in the study. TRAIL and TRAIL receptor expression profiles were determined by immunohistochemistry. Annexin V binding revealed the apoptotic index in pancreas. Lastly, the tumor grade, tumor stage, tumor diameter, perineural invasion, and number of lymph node metastasis were used for comparison purposes.


RESULTS
TRAIL decoy receptor 2 (DcR2) and death receptor 4 expression were up-regulated in PDAC patients compared with noncancer patients, and the ductal cells of PDAC patients displayed significant levels of apoptosis. In addition, acinar cells from PDAC patients had higher DcR2 expression but lower death receptor 4 expression. Increased DcR2 expression was also observed in Langerhans islets of PDAC patients.


CONCLUSIONS
Differential alteration of TRAIL and TRAIL receptor expression profiles in PDAC patients suggest that the TRAIL/TRAIL receptor system may play a pivotal role during pancreatic carcinoma development.
Sanlioglu
Ahter Dilsad
AD
Department of Medical Biology and Genetics, Faculty of Medicine, Human Gene Therapy Unit, Akdeniz University, Antalya, Turkey. sanlioglu@akdeniz.edu.tr
Dirice
Ercument
E
Elpek
Ozlem
O
Korcum
Aylin Fidan
AF
Ozdogan
Mustafa
M
Suleymanlar
Inci
I
Balci
Mustafa Kemal
MK
Griffith
Thomas S
TS
Sanlioglu
Salih
S
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000737:chemistry; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000502:physiology*; D053319:Tumor Necrosis Factor Decoy Receptors / Q000032:analysis / Q000502:physiology*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors