PMID- 19054610 OWN - NLM STAT- MEDLINE DCOM- 20090318 LR - 20131121 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 276 IP - 1 DP - 2009 Apr 8 TI - Okadaic acid promotes angiogenesis via activation of hypoxia-inducible factor-1. PG - 102-8 LID - 10.1016/j.canlet.2008.10.034 [doi] AB - Okadaic acid, a potent tumor promoter and an inhibitor of protein phosphatase 1 and 2A, has also been characterized as an angiogenic inducer in the chorioallantoic membrane of the chick embryo. To elucidate the roles of okadaic acid on angiogenic processes, we conducted in vitro angiogenesis assays. In this study, we report that okadaic acid potently stimulated tube formation, migration, and invasion of human umbilical vein endothelial cells. Moreover, okadaic acid elevated the activities of hypoxia-inducible factor-1 (HIF-1), which is closely related with the expression of vascular endothelial growth factor. Exposure to okadaic acid markedly increased the HIF-1alpha protein level through up-regulation of translation via activation of Akt and mTOR pathway. Taken together, these results demonstrated that okadaic acid promotes angiogenesis through stimulation of Akt mediated HIF-1alpha translation. FAU - Kim, Young-Sun AU - Kim YS AD - Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. FAU - Ahn, Kook-Hee AU - Ahn KH FAU - Kim, Seon-Ye AU - Kim SY FAU - Jeong, Joo-Won AU - Jeong JW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081202 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Carcinogens) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Vascular Endothelial Growth Factor A) RN - 1W21G5Q4N2 (Okadaic Acid) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Angiogenesis Inducing Agents/*pharmacology MH - Blotting, Western MH - Carcinogens/pharmacology MH - Cell Movement/drug effects MH - Endothelial Cells/drug effects MH - Fluorescent Antibody Technique MH - Gene Expression Regulation/*drug effects MH - HeLa Cells MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*drug effects/metabolism MH - Immunohistochemistry MH - Neovascularization, Physiologic/drug effects/*physiology MH - Okadaic Acid/*pharmacology MH - Protein Biosynthesis MH - Proto-Oncogene Proteins c-akt/biosynthesis/drug effects MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transfection MH - Umbilical Veins/drug effects MH - Vascular Endothelial Growth Factor A/biosynthesis/drug effects EDAT- 2008/12/05 09:00 MHDA- 2009/03/19 09:00 CRDT- 2008/12/05 09:00 PHST- 2008/09/24 00:00 [received] PHST- 2008/10/27 00:00 [revised] PHST- 2008/10/27 00:00 [accepted] PHST- 2008/12/05 09:00 [pubmed] PHST- 2009/03/19 09:00 [medline] PHST- 2008/12/05 09:00 [entrez] AID - S0304-3835(08)00859-8 [pii] AID - 10.1016/j.canlet.2008.10.034 [doi] PST - ppublish SO - Cancer Lett. 2009 Apr 8;276(1):102-8. doi: 10.1016/j.canlet.2008.10.034. Epub 2008 Dec 2.