Lipoxygenase-5 is overexpressed in prostate adenocarcinoma

BAGKGROUND. Epidemiologic studies suggest that populations that consume lar ge amounts of dietary fat are at greater risk for prostate carcinoma. Arach idonic acid and its precursor, linoleic acid, are major ingredients of anim al fats and many vegetable oils that are used in the regions where prostate carcinoma is prevalent. The metabolism of arachidonic acid by either the c yclooxygenase pathway or the lipoxygenase pathway generates eicosanoids, wh ich have been implicated in the pathogenesis of a variety of human diseases , including cancer, and are now believed to play important roles in tumor p romotion, progression, and metastasis. Studying these pathways in specimens from patients with prostate carcinoma, the authors recently demonstrated t he overexpression of cyclooxygenase-2 in prostate adenocarcinoma. In the cu rrent 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 expressi on of 5-LO was determined using reverse transcriptase-polymerase chain reac tion, immunoblotting, and immunohistochemistry and by measuring the levels of 5-hydroxyeicosatetraenoic acid (5-METE) by radioimmunoassay. RESULTS. The mean level of 5-LO mRNA was six-fold greater (P < 0.001) in ma lignant tissue compared with benign tissue. The immunoblot analysis demonst rated 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-ME TE, which is a metabolic product of arachidonic acid, was found to be 2.2-f old greater (P < 0.001) in malignant tumor tissue compared with benign tiss ue. CONCLUSIONS. To the authors' knowledge, this is the first in vivo study sho wing overexpression of 5-LO in patients with prostate carcinoma. This study suggests that inhibitors of arachidonic acid pathway in general and select ive 5-LO inhibitors in particular may be useful for prevention or therapy i n patients with prostate carcinoma. (C) 2001 American Cancer Society.