Several types of
lipoxygenases with various functions occur in mammalian cells. Although the presence of
12-lipoxygenase activity has been reported in uterine tissues, neither its type nor its
biological functions have yet been established. Moreover, the putative role of uterine
12-lipoxygenase in
cervical cancer has not been addressed before. Homogenates of uterine tissues from women without
cancer and from patients with invasive cervical
carcinoma were incubated with (1-(14)C)-arachidonic
acid under various conditions and the labelled reaction products were analyzed both by thin-layer chromatography and by high-pressure liquid chromatography.
12-Lipoxygenase protein was estimated by Western blot using anti-serum against recombinant human platelet-type
12-lipoxygenase. Highest concentrations and activities of
12-lipoxygenase were found in the exocervix. The formation of 12S-hydroxy-5Z,8Z,10E, 14Z-eicosatetraenoic
acid (12-HETE) was stimulated by micromolar concentrations of 13S-hydroperoxy-9Z,11E-octadecadienoic
acid, suggesting metabolic control of the
12-lipoxygenase activity via the
hydroperoxide tone. Immunohistochemical investigation revealed that the
enzyme is mainly located in the squamous epithelium, and is of platelet-type. Significantly lower values for the
12-HETE formation were found in samples from patients with invasive cervical
carcinoma, whereas the amount of immunochemically detectable
12-lipoxygenase protein was unaltered. At the same time the expression levels of the bcl-2 gene were enhanced. Thus, it is concluded that during
carcinogenesis the
hydroperoxide-reducing capacity of the uterine cervix tissue is enhanced, possibly mediated by bcl-2
protein, and in turn metabolically suppresses the
12-lipoxygenase activity. Furthermore, the data suggest an anti-carcinogenic action of
12-lipoxygenase in human cervix, in contrast to its reported pro-carcinogenic action in
breast cancer.