Expression of 15-lipoxygenase-1 in human colorectal cancer

Recently we reported the induction of reticulocyte type 15-lipoxygenase I ( 19-Lox-1) in a human colorectal carcinoma cell line that had been stimulate d by butyrate to undergo apoptosis and cell differentiation (H. Kamitani et al., J, Biol, Chem., 273: 21569-21577, 1998), To determine if TS-Los-l is expressed in human colorectal cancer tissue, 21 matched pairs of colorectal tumor and adjacent normal tissue were examined by immunoblot analysis usin g specific antibodies for human 15-Lox-1, prostaglandin H synthase (also ra iled cyclooxygenase, Cox)-1 and Cox-2. Eighteen of the 21 were found to hav e 15-Lorr-1 in both tumor tissue and matched adjacent normal tissue, with t he 15-Lox-1 expression being significantly higher in most of the tumor tiss ue. The expression of Cox-2 was also elevated in most tumors, whereas Cox-1 was frequently expressed at lower levels in the tumor tissue than in the p aired normal tissue Reverse-phase high-performance liquid chromatography an alysis of arachidonate metabolites, formed on incubation of arachidonic aci d with a crude enzyme preparation from the colon samples, revealed the form ation of 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid with a much lower l evel of 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (15-hydroxy-5Z,8Z,11 Z,13E-eicosatetraenoic acid:12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid, 6.5:1) which also indicate the presence of 15-Lox-1. Furthermore, reverse transcription-PCR with primers specific for human 15-Lox-1 or 15-Lox-2 cDNA indicated that 15-Lox-1 mRNA was present in the colorectal tumors. The seq uence of the PCR product was identical to the human 15-Lox-1. Immunohistoch emical studies showed 15-Lox-1 localization in the glandular epithelium of human colorectal tumor tissue. These results suggest that 15-Lox-1 is highl y expressed in human colorectal canter epithelial cells and that its expres sion may have a role in colorectal carcinogenesis.