%0 Journal Article %1 Koyanagi.2003 %A Koyanagi, S. %A Kuramoto, Y. %A Nakagawa, H. %A Aramaki, H. %A Ohdo, S. %A Soeda, S. %A Shimeno, H. %D 2003 %J Cancer Res. %K & (Genetics) 1 A Angiogenesis Animals Aryl Cell Circadian Cycle DNA-Binding Drosophila Endothelial Expression Eye Factor Factors Flavoproteins G-Protein-Coupled Gene Genetic Growth Hydrocarbon Hypoxia Hypoxia-Inducible ICR Inbred Inhibitors Invertebrate Japan Male Messenger Mice Neoplastic Nuclear Photoreceptors Promoter Proteins RNA Receptor Receptors Regions Regulation Research Rhythm Subunit Transcription Transfection Translocator Vascular alpha analysis antagonists biosynthesis cells genetics inhibitors metabolism pharmacology physiology protein response therapy %N 21 %P 7277-7283 %T A molecular mechanism regulating circadian expression of vascular endothelial growth factor in tumor cells %U PM:14612524 %V 63 %X Because angiogenesis is essential for tumor growth and metastasis, inhibition of angiogenesis has emerged as a new therapy to treat cancers. Hypoxia-induced expression of vascular endothelial growth factor (VEGF) plays a central role in tumor-induced angiogenesis. In this study, we found that expression of VEGF in hypoxic tumor cells was affected by the circadian organization of molecular clockwork. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop in which CLOCK and BMAL1 are positive regulators, and Period and Cryptochrome genes act as negative ones. The levels of VEGF mRNA in tumor cells implanted in mice rose substantially in response to hypoxia, but the levels fluctuated rhythmically in a circadian fashion. Luciferase reporter gene analysis revealed that Period2 and Cryptochrome1, whose expression in the implanted tumor cells showed a circadian oscillation, inhibited the hypoxia-induced VEGF promoter activity. These results sugg

@article{Koyanagi.2003, abstract = {Because angiogenesis is essential for tumor growth and metastasis, inhibition of angiogenesis has emerged as a new therapy to treat cancers. Hypoxia-induced expression of vascular endothelial growth factor (VEGF) plays a central role in tumor-induced angiogenesis. In this study, we found that expression of VEGF in hypoxic tumor cells was affected by the circadian organization of molecular clockwork. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop in which CLOCK and BMAL1 are positive regulators, and Period and Cryptochrome genes act as negative ones. The levels of VEGF mRNA in tumor cells implanted in mice rose substantially in response to hypoxia, but the levels fluctuated rhythmically in a circadian fashion. Luciferase reporter gene analysis revealed that Period2 and Cryptochrome1, whose expression in the implanted tumor cells showed a circadian oscillation, inhibited the hypoxia-induced VEGF promoter activity. These results sugg}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Koyanagi, S. and Kuramoto, Y. and Nakagawa, H. and Aramaki, H. and Ohdo, S. and Soeda, S. and Shimeno, H.}, biburl = {https://www.bibsonomy.org/bibtex/235d6ce1ed81e98eff764cd4eb2f9a78a/kanefendt}, interhash = {6ba4e746e4cb45f0627d435c671eb840}, intrahash = {35d6ce1ed81e98eff764cd4eb2f9a78a}, journal = {Cancer Res.}, keywords = {& (Genetics) 1 A Angiogenesis Animals Aryl Cell Circadian Cycle DNA-Binding Drosophila Endothelial Expression Eye Factor Factors Flavoproteins G-Protein-Coupled Gene Genetic Growth Hydrocarbon Hypoxia Hypoxia-Inducible ICR Inbred Inhibitors Invertebrate Japan Male Messenger Mice Neoplastic Nuclear Photoreceptors Promoter Proteins RNA Receptor Receptors Regions Regulation Research Rhythm Subunit Transcription Transfection Translocator Vascular alpha analysis antagonists biosynthesis cells genetics inhibitors metabolism pharmacology physiology protein response therapy}, number = 21, pages = {7277-7283}, timestamp = {2010-02-05T11:28:40.000+0100}, title = {A molecular mechanism regulating circadian expression of vascular endothelial growth factor in tumor cells}, url = {PM:14612524}, volume = 63, year = 2003 }