Lipoxygenase-5 is overexpressed in prostate adenocarcinoma.
BACKGROUND
Epidemiologic studies suggest that populations that consume large amounts of dietary fat are at greater risk for prostate carcinoma. Arachidonic acid and its precursor, linoleic acid, are major ingredients of animal fats and many vegetable oils that are used in the regions where prostate carcinoma is prevalent. The metabolism of arachidonic acid by either the cyclooxygenase pathway or the lipoxygenase pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including cancer, and are now believed to play important roles in tumor promotion, progression, and metastasis. Studying these pathways in specimens from patients with prostate carcinoma, the authors recently demonstrated the overexpression of cyclooxygenase-2 in prostate adenocarcinoma. In the current study, the authors report the overexpression of lipoxygenase-5 (5-LO) in samples from patients with prostate adenocarcinoma.


METHODS
Employing 22 pair-matched benign and malignant tissue samples that were obtained from the same patients with prostate carcinoma, the expression of 5-LO was determined using reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry and by measuring the levels of 5-hydroxyeicosatetraenoic acid (5-HETE) by radioimmunoassay.


RESULTS
The mean level of 5-LO mRNA was six-fold greater (P < 0.001) in malignant tissue compared with benign tissue. The immunoblot analysis demonstrated that, compared with benign tissue, 5-LO protein was overexpressed in 16 of 22 samples examined and was 2.6 fold greater (P < 0.001) in malignant tissue. Immunohistochemical studies further verified 5-LO up-regulation in malignant tissue that was not present in benign tissue. The levels of 5-HETE, which is a metabolic product of arachidonic acid, was found to be 2.2-fold greater (P < 0.001) in malignant tumor tissue compared with benign tissue.


CONCLUSIONS
To the authors' knowledge, this is the first in vivo study showing overexpression of 5-LO in patients with prostate carcinoma. This study suggests that inhibitors of arachidonic acid pathway in general and selective 5-LO inhibitors in particular may be useful for prevention or therapy in patients with prostate carcinoma.
Department of Dermatology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
S
S
Gupta
M
M
Srivastava
N
N
Ahmad
K
K
Sakamoto
D G
DG
Bostwick
H
H
Mukhtar
D000230:Adenocarcinoma / Q000201:enzymology* / Q000378:metabolism; D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006893:Hydroxyeicosatetraenoic Acids; D012333:RNA, Messenger; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D001094:Arachidonate 5-Lipoxygenase