Journal
CANCER LETTERS
Volume 276, Issue 1, Pages 102-108Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.10.034
Keywords
Okadaic acid; Angiogenesis; HIF-1 alpha; Akt
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Funding
- Korea Science and Engineering Foundation [R13-2002-020-02003-0(2007)]
- National Research Foundation of Korea [R13-2002-020-02003-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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-1 alpha 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-1 alpha translation. Crown Copyright (C) 2008 Published by Elsevier Ireland Ltd. All rights reserved.
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