Downregulation of tumstatin expression by overexpression of ornithine decarboxylase

Wang,Wei; Xu,Chun-Xiao; Hou,Guo-Sheng; Chen,You-Gen; Xin,Jia-Xuan; Liu,Xian-Xi

doi:10.3892/or.2013.2708

Downregulation of tumstatin expression by overexpression of ornithine decarboxylase

Authors:
- Wei Wang
- Chun-Xiao Xu
- Guo-Sheng Hou
- You-Gen Chen
- Jia-Xuan Xin
- Xian-Xi Liu
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Affiliations: Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Shandong Center for Disease Control and Prevention, Jinan, Shandong 250014, P.R. China, Quangang Pharmaceutical (SD) Co., Ltd., Jinan, Shandong 250014, P.R. China, Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Institute of Medical Molecular Genetics, Department of Biochemistry and Molecular Biology, Bin Zhou Medical University, Lai Shan, Yan Tai, Shandong 264003, P.R. China
Published online on: August 29, 2013 https://doi.org/10.3892/or.2013.2708
Pages: 2042-2048
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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