title: Downregulation of tumstatin expression by overexpression of ornithine decarboxylase.
abstract: Tumor angiogenesis, a pivotal process for cancer growth and metastasis, requires both upregulation of pro‑angiogenic molecules and downregulation of anti‑angiogenic molecules. Anti-angiogenesis therapy represents a promising way for cancer treatment. Tumstatin, a novel endogenous angiogenesis inhibitor, inhibits endothelial cell proliferation, pathological angiogenesis and tumor growth. Ornithine decarboxylase (ODC), overexpressed in various cancers, is associated with cell transformation, tumor invasion and angiogenesis. We found that the expression of tumstatin was suppressed in ODC-overexpressing human cancer cells and renal carcinoma tissues. We presumed that ODC overexpression may downregulate the expression of tumstatin. To be able to test this hypothesis, we generated HEK293 cells that overexpress ODC (ODC transfectants) and characterized the following experimental groups: PBS-treated group, mock transfectants, ODC transfectants, ODC transfectants transfected with pcDNA-ODCr (an antisense ODC-expressing plasmid) group and putrescine-treated group. The effect of ODC overexpression on tumstatin expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot analysis and dual luciferase reporter assay. ODC-overexpressing cells and putrescine-treated cells showed suppressed tumstatin mRNA and protein expression, and decreased tumstatin gene promoter activity. Thus, ODC overexpression suppresses the expression of tumstatin, which may provide fundamental evidence for the combination of anti-angiogenic therapy and conventional therapy for cancer treatment.
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Chun-Xiao
authors.initials: CX
authors.lastname: Xu
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Hou
authors.forename: You-Gen
authors.initials: YG
authors.lastname: Chen
authors.forename: Jia-Xuan
authors.initials: JX
authors.lastname: Xin
authors.forename: Xian-Xi
authors.initials: XX
authors.lastname: Liu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D001324:Autoantigens / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D024141:Collagen Type IV / Q000008:administration & dosage*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain; D009955:Ornithine Decarboxylase