5-Lipoxygenase and leukotriene B(4) receptor are expressed in human pancreatic cancers but not in pancreatic ducts in normal tissue.
The 5-lipoxygenase (5-LOX) pathway is critical for pancreatic cancer cell growth and escape from apoptosis. Inhibition of 5-LOX blocks proliferation and induces apoptosis in human pancreatic cancer cells. However, the expression of 5-LOX and its downstream signaling pathway have not been investigated in human pancreatic adenocarcinoma. Reverse transcriptase-polymerase chain reaction revealed expression of 5-LOX mRNA in all pancreatic cancer cell lines tested including, PANC-1, AsPC-1, and MiaPaCa2 cells, but not in normal pancreatic ductal cells. The expression of 5-LOX protein in pancreatic cancer cell lines was demonstrated by Western blotting. Finally, 5-LOX up-regulation in human pancreatic cancer tissues was verified by intense positive staining in cancer cells by immunohistochemistry. Staining for the 5-LOX protein was particularly evident in the ductal components of the more differentiated tumors but not in ductal cells in normal pancreatic tissues from cadaver donors. Immunohistochemistry also revealed strong staining of cancer tissues with an antibody to the receptor of the downstream 5-LOX metabolite, leukotriene B(4). The current study demonstrated marked expression of 5-LOX and the leukotriene B(4) receptor in human pancreatic cancer tissues. These findings provide further evidence of up-regulation of this pathway in pancreatic cancer and that LOX inhibitors are likely to be valuable in the treatment of this dreadful disease.
Hennig
René
R
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Ding
Xian-Zhong
XZ
Tong
Wei-Gang
WG
Schneider
Matthias B
MB
Standop
Jens
J
Friess
Helmut
H
Büchler
Markus W
MW
Pour
Parviz M
PM
Adrian
Thomas E
TE
D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis*; D014408:Biomarkers, Tumor; D006801:Humans; D007150:Immunohistochemistry; D010183:Pancreatic Ducts / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D018102:Receptors, Leukotriene B4 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018102:Receptors, Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase