Mechanisms Regulating Tumor Angiogenesis by 12-Lipoxygenase in Prostate Cancer Cells
| Autor: | Kenneth V. Honn, Alex Zacharek, Daotai Nie, Julie Milanini, Rongxian Jin, Gilles Pagès, Keqin Tang, Yande Guo, Yan Qiao, YuChyu Chen, Sriram Krishnamoorthy |
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| Přispěvatelé: | Depts of Radiation Oncology and Pathology, Wayne State University [Detroit]-Karmanos Cancer Institute, The division of Applied Mathematics [Providence], Brown University, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ) |
| Rok vydání: | 2006 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Angiogenesis medicine.disease_cause Biochemistry [ SDV.CAN ] Life Sciences [q-bio]/Cancer Metastasis Phosphatidylinositol 3-Kinases 0302 clinical medicine Cell Movement MESH : 1-Phosphatidylinositol 3-Kinase MESH : Cell Movement 12-Hydroxy-5 8 10 14-eicosatetraenoic Acid Lipoxygenase Inhibitors Promoter Regions Genetic MESH: Cell Movement Phosphoinositide-3 Kinase Inhibitors MESH: 12-Hydroxy-5 8 10 14-eicosatetraenoic Acid 0303 health sciences Neovascularization Pathologic MESH : 12-Hydroxy-5 8 10 14-eicosatetraenoic Acid MESH: Gene Expression Regulation Neoplastic Transfection MESH: Flavanones 3. Good health Gene Expression Regulation Neoplastic Endothelial stem cell MESH: Promoter Regions (Genetics) 030220 oncology & carcinogenesis Flavanones MESH : Lipoxygenase Inhibitors MESH : Vascular Endothelial Growth Factor A MESH: Endothelium Vascular MESH : Prostatic Neoplasms MESH: Cell Line Tumor MESH : Gene Expression Regulation Neoplastic Morpholines MESH : Male MESH : Arachidonate 12-Lipoxygenase MESH: Morpholines [SDV.CAN]Life Sciences [q-bio]/Cancer [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Biology Arachidonate 12-Lipoxygenase MESH: Arachidonate 12-Lipoxygenase MESH: Lipoxygenase Inhibitors 03 medical and health sciences Cell Line Tumor medicine Humans Masoprocol Luciferase Northern blot Molecular Biology 030304 developmental biology MESH: Humans MESH : Nordihydroguaiaretic Acid MESH : Cell Line Tumor MESH : Flavanones MESH: Vascular Endothelial Growth Factor A MESH : Humans Prostatic Neoplasms MESH : Neovascularization Pathologic [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology MESH: 1-Phosphatidylinositol 3-Kinase Cell Biology medicine.disease MESH : Promoter Regions (Genetics) Molecular biology MESH: Male MESH: Chromones HIF1A Chromones MESH : Endothelium Vascular MESH: Prostatic Neoplasms MESH: Nordihydroguaiaretic Acid Endothelium Vascular MESH: Neovascularization Pathologic Carcinogenesis MESH : Chromones MESH : Morpholines |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2006, 281 (27), pp.18601-9. ⟨10.1074/jbc.M601887200⟩ Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2006, 281 (27), pp.18601-9. 〈10.1074/jbc.M601887200〉 |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.m601887200 |
| Popis: | International audience; 12-Lipoxygenase utilizes arachidonic acid to synthesize 12(S)-hydroperoxyeicosatetraenoic acid, which is converted to the end product 12(S)-hydroxyeicosatetraenoic acid, an eicosanoid that promotes tumorigenesis and metastasis. Increased expression of 12-lipoxygenase has been documented in a number of carcinomas. When overexpressed in human prostate or breast cancer, 12-lipoxygenase promotes tumor angiogenesis and growth in vivo. The present study was undertaken to delineate the mechanisms by which 12-lipoxygenase enhances angiogenesis. Herein we report that nordihydroguaiaretic acid, a pan inhibitor of lipoxygenases and baicalein, a selective inhibitor of 12-lipoxygenase, reduced VEGF expression in human prostate cancer PC-3 cells. Overexpression of 12-lipoxygenase in PC-3 cells resulted in a 3-fold increase in VEGF protein level when compared with vector control cells. An increase in PI 3-kinase activity was found in 12-LOX-transfected PC-3 cells and inhibition of PI 3-kinase by LY294002 significantly reduced VEGF expression. Northern blot and real time PCR analyses revealed an elevated VEGF transcript level in PC-3 cells transfected with a 12-lipoxygenase expression construct. Using a VEGF promoter luciferase construct (-1176/+54), we found a 10-fold increase in VEGF promoter activity in 12-lipoxygenase-transfected PC-3 cells. The region located between -88 and -66 of the VEGF promoter was identified as 12-lipoxygenase responsive using VEGF promoter-based luciferase assays. Further analysis with mutant constructs indicated Sp1 as a transcription factor required for 12-lipoxygenase stimulation of VEGF. Neutralization of VEGF by a function-blocking antibody significantly decreased the ability of 12-lipoxygenase-transfected PC-3 cells to stimulate endothelial cell migration, suggesting VEGF as an important effector for 12-lipoxygenase-mediated stimulation of tumor angiogenesis. |
| Databáze: | OpenAIRE |
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