title: Inhibition of carcinogenesis in transgenic mouse models over-expressing 15-lipoxygenase in the vascular wall under the control of murine preproendothelin-1 promoter.
abstract: Oxygenases are a family of enzymes that dioxygenate unsaturated fatty acids, thus initiating membrane oxidation and signaling molecule synthesis. The lipoxygenases (LOs), a family of lipid-peroxidizing enzymes that induce structural and metabolic changes in the cell in a number of pathophysiological conditions, belong to the oxygenases family. This class of enzymes has several subgroups, named 5-, 8-, 12- and 15-LOs, and these LO-isoforms are capable of oxygenating arachidonic and linoleic acid. 15-LOs were reported to play an inhibitory role in tumor angiogenesis and, consequently, they slow down carcinogenesis. It has been suggested that its anti-carcinogenic effect is conferred by promoting cell differentiation and apoptosis. Using transgenic mice that over-express 15-LO-1 in endothelial cells under the regulation of the murine preproendothelin-1 promoter, we studied its effect on tumor and metastasis growth. We found that 15-LO-1 inhibited tumor and metastasis growth in the transgenic mice in two different models of cancer (mammary gland and Lewis lung carcinoma). This inhibition was concomitant with a higher number of apoptotic cells in the metastases of the transgenic mice and with a complicated network of multiple small blood vessels. This finding targets 15-LO as a new candidate in the treatment of carcinogenesis.
authors.affiliation: Institute of Lipid and Atherosclerosis Research, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, 52621 Hashomer Tel, Israel. dharats@post.tau.ac.il
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
authors.forename: Dikla
authors.initials: D
authors.lastname: Ben-Shushan
authors.forename: Hofit
authors.initials: H
authors.lastname: Cohen
authors.forename: Ayelet
authors.initials: A
authors.lastname: Gonen
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Iris
authors.initials: I
authors.lastname: Goldberg
authors.forename: Shoshana
authors.initials: S
authors.lastname: Greenberger
authors.forename: Israel
authors.initials: I
authors.lastname: Hodish
authors.forename: Ayelet
authors.initials: A
authors.lastname: Harari
authors.forename: Nira
authors.initials: N
authors.lastname: Varda-Bloom
authors.forename: Keren
authors.initials: K
authors.lastname: Levanon
authors.forename: Ehud
authors.initials: E
authors.lastname: Grossman
authors.forename: Pavlos
authors.initials: P
authors.lastname: Chaitidis
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kühn
authors.forename: Aviv
authors.initials: A
authors.lastname: Shaish
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D001808:Blood Vessels; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000235:genetics / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019332:Endothelin-1 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; D001093:Arachidonate 15-Lipoxygenase