Expression analysis of the prostaglandin E2 production pathway in human pancreatic cancers.
OBJECTIVE
There is strong evidence for an important role of cyclooxygenase (COX) 2 and COX-2-generated PGE2 during pancreatic tumorigenesis. Cyclooxygenase 2 has therefore become a potential chemotherapeutic target for pancreatic cancer. However, recent studies raised concerns regarding the safety of selective COX-2 inhibitors. Although the benefits of COX-2 inhibition may eventually outweigh the associated cardiovascular risks, there are a number of alternative targets for inhibiting the formation of PGE2 in human tumors that may prove less harmful to the patient. This study aimed at analyzing the expression of various proteins involved in the generation of PGE2 in human pancreatic cancers.


RESULTS
Real-time polymerase chain reaction and Western blot analyses demonstrated overexpression of cytoplasmic phospholipase A2, COX-2, cytoplasmic prostaglandin E synthase, and microsomal prostaglandin E synthases 1 and 2 in most human pancreatic cancers when compared with matched normal pancreas. Immunohistochemistry revealed expression of these proteins predominantly by pancreatic cancer cells. Variable expression of these proteins was also confirmed in several human pancreatic cancer cell lines.


CONCLUSIONS
Our studies demonstrated for the first time that various proteins involved in the generation of PGE2 are overexpressed in human pancreatic cancers. These proteins may represent potentially novel targets for the therapy of pancreatic cancers.
Hasan
Sascha
S
Department of Surgery, Hirshberg Laboratories for Pancreatic Cancer Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Satake
Makoto
M
Dawson
David W
DW
Funahashi
Hitoshi
H
Angst
Eliane
E
Go
Vay Liang W
VL
Reber
Howard A
HA
Hines
Oscar J
OJ
Eibl
Guido
G
D001483:Base Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis*; D015870:Gene Expression; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051546:Cyclooxygenase 2; D054467:Phospholipases A2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone