Regulation of 12-Lipoxygenase Expression by Epidermal Growth Factor in Human Epidermoid Carcinoma A431 Cells

Abstract

Arachidonate 12-lipoxygenase in the platelet was the first mammalian lipoxygenase discoverved¹. It catalyzes the transformation of arachidonic acid into 12(S)-hydroperoxyeicosatetraenoic acid, which is subsequently converted to 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) by a glutathione-dependent peroxidase². We recently identified a human 12-lipoxygenase as the platelet-type enzyme in human epidermoid carcinoma A431 cells, and found that epidermal growth factor (EGF) increased the 12-lipoxygenase mRNA level by about 2-fold with a lag peroid of 10 h, which was parallel to the increase in enzyme activity³. This was the first evidence indicating the inducibility of a human 12-lipoxygenase gene expression by growth factor. In studying the signal transduction of EGF in the induction of 12-lipoxygenase expression, we recently reported the possible involvement of protein kinase C activation in the expression of EGF-induced 12-lipxoygenase⁴. The biological activities of 12(S)-HETE induces the expression of glycoprotein Ilb-IIIa on the cell membrane of Lewis lung carcinoma cells⁵ and may also play a significant role in the pathogenesis of some epidermal and epithelial inflammation⁶. Takahashi et al.⁷ identified 12-lipoxygenase in human epidermal cells as a platelet-type enzyme and Hussain et al.⁸ recently found an overexpression of the human platelet-type 12-lipoxygenase in germinal layer keratinocytes in psoriasis.