Eicosanoid 12(S)-HETE Activates Phosphatidylinositol 3-Kinase

The arachidonic acid metabolite of 12 lipoxygenase, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) promotes metastatic behavior of tumor cells. In this study we set out to identify 12(S)-HETE signaling pathways, and their contribution to cellular functions in A431 epidermoid carcinoma. (1) 12(S)-HE...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2000-08, Vol.275 (2), p.690-695
Main Authors: Szekeres, Charles K., Trikha, Mohit, Nie, Daotai, Honn, Kenneth V.
Format: Article
Language:English
Subjects:
12(S)-HETE
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - metabolism
eicosanoid
Enzyme Activation
ERK
Humans
Isoenzymes - metabolism
MAPK
migration
Mitogen-Activated Protein Kinases - metabolism
Phosphatidylinositol 3-Kinases - metabolism
PI3 kinase
PKC
Protein Kinase C - metabolism
Signal Transduction
Tumor Cells, Cultured
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Summary:The arachidonic acid metabolite of 12 lipoxygenase, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) promotes metastatic behavior of tumor cells. In this study we set out to identify 12(S)-HETE signaling pathways, and their contribution to cellular functions in A431 epidermoid carcinoma. (1) 12(S)-HETE stimulated phosphotyrosine associated PI3 kinase activity. (2) 12(S)-HETE stimulated ERK1/2 in a PI3 kinase dependent manner. (3) PI3 kinase affected the 12(S)-HETE stimulated Raf/MEK/ERK cascade at the level of MEK. (4) 12(S)-HETE stimulated ERK1/2 via PKCĪ¶. (5) 12(S)-HETE stimulated cell migration on laminin, which was eliminated by PI3 kinase and cPKC inhibitors, but it was unaffected by inhibition of ERK1/2.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2000.3348