Gupta S, Srivastava M, Ahmad N, Sakamoto K, Bostwick D G, Mukhtar H
Department of Dermatology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
Cancer. 2001 Feb 15;91(4):737-43. doi: 10.1002/1097-0142(20010215)91:4<737::aid-cncr1059>3.0.co;2-f.
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.
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.
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.
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.
流行病学研究表明，大量摄入膳食脂肪的人群患前列腺癌的风险更高。花生四烯酸及其前体亚油酸是动物脂肪和许多植物油的主要成分，而前列腺癌高发地区的人们常用这些油脂。花生四烯酸通过环氧合酶途径或脂氧合酶途径代谢生成类二十烷酸，这些类二十烷酸与包括癌症在内的多种人类疾病的发病机制有关，现在认为它们在肿瘤促进、进展和转移中起重要作用。在对前列腺癌患者的标本进行这些途径的研究时，作者最近证明了环氧合酶-2在前列腺腺癌中的过度表达。在本研究中，作者报告了脂氧合酶-5（5-LO）在前列腺腺癌患者样本中的过度表达。
采用从同一前列腺癌患者获取的22对匹配的良性和恶性组织样本，使用逆转录聚合酶链反应、免疫印迹和免疫组织化学测定5-LO的表达，并通过放射免疫测定法测量5-羟基二十碳四烯酸（5-HETE）的水平。
与良性组织相比，恶性组织中5-LO mRNA的平均水平高6倍（P < 0.001）。免疫印迹分析表明，与良性组织相比，在检测的22个样本中的16个中5-LO蛋白过度表达，并且在恶性组织中高2.6倍（P < 0.001）。免疫组织化学研究进一步证实了恶性组织中5-LO的上调，而良性组织中不存在这种上调。发现花生四烯酸的代谢产物5-HETE的水平在恶性肿瘤组织中比良性组织高2.2倍（P < 0.001）。
据作者所知，这是第一项显示5-LO在前列腺癌患者中过度表达的体内研究。这项研究表明，一般而言，花生四烯酸途径抑制剂，特别是选择性5-LO抑制剂可能对前列腺癌患者的预防或治疗有用。
