5-Lipoxygenase, a marker for early pancreatic intraepithelial neoplastic lesions.
Pancreatic cancer has an abysmal prognosis because of late diagnosis. Therefore, it is important to identify risk factors if we are to be able to prevent and detect this cancer in an early, noninvasive stage. Pancreatic intraepithelial neoplasias (PanIN) are the precursor lesions which could be an ideal target for chemoprevention. This study shows up-regulation of 5-lipoxygenase (5-LOX) in all grades of human PanINs and early lesions of pancreatic cancer in two different animal models (EL-Kras mice and N-nitrosobis(2-oxopropyl)amine-treated hamsters) by immunohistochemistry. The results were consistent in all tissues examined, including seven chronic pancreatitis patients, four pancreatic cancer patients, one multiorgan donor, nine EL-Kras mice, and three N-nitrosobis(2-oxopropyl)amine-treated hamsters, all with PanINs. Overexpression of 5-LOX in NIH3T3 cells resulted in greater sensitivity of these cells to the growth inhibitory effects of the 5-LOX inhibitor Rev5901. These findings provide evidence that 5-LOX plays a key role in the development of pancreatic cancer. Furthermore, the lipoxygenase pathway may be a target for the prevention of this devastating disease.
Hennig
Rene
R
Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Grippo
Paul
P
Ding
Xian-Zhong
XZ
Rao
Sambasiva M
SM
Buchler
Markus W
MW
Friess
Helmut
H
Talamonti
Mark S
MS
Bell
Richard H
RH
Adrian
Thomas E
TE
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D002273:Carcinogens; D002278:Carcinoma in Situ / Q000201:enzymology / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D002908:Chronic Disease; D006224:Cricetinae; D006801:Humans; D007150:Immunohistochemistry; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D010195:Pancreatitis / Q000201:enzymology / Q000473:pathology; D011804:Quinolines / Q000494:pharmacology
D014408:Biomarkers, Tumor; D002273:Carcinogens; D016859:Lipoxygenase Inhibitors; D009602:Nitrosamines; D011804:Quinolines; C049740:alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; C013622:nitrosobis(2-oxopropyl)amine; D001094:Arachidonate 5-Lipoxygenase