12-Lipoxygenase in human tumor cells

Tumor cell proliferation and metastasis proceed via a network of interdependent molecular events with a vast array of molecular players and signal transduction mechanisms differing in various types of human tumors. In the sequence of events necessary for carcinogenesis, arachidonate metabolites have been documented to play a significant role at several steps. Arachidonate metabolism in human cells occurs via several enzymatic pathways, including enzymes such as cyclo-oxygenases and lipoxygenases. This review pays particular attention to one member of the lipoxygenase family of enzymes, namely 12-lipoxygenase, since an arachidonate metabolite generated via 12-lipoxygenase action, 12(S)-HETE, has been shown to elicit various prometastatic effects of tumor cells in vivo and in vitro. We focus especially on mechanisms of activation and modulation of 12-lipoxygenase expression in human tumor cells, since various tumor cells express 12-lipoxygenase or are responsive to metabolites derived from 12-lipoxygenase action, thus offering a potential for successful therapeutic intervention against such tumors