Metabolic suppression of platelet-type 12-lipoxygenase in human uterine cervix with invasive carcinoma
✍ Scribed by Santosh Nigam; G. Sravan Kumar; Mark Sutherland; Tankred Schewe; Hiroshi Ikawa; Yoshikazu Yamasaki; Natsuo Ueda; Shozo Yamamoto
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 120 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
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 thinlayer chromatography and by high-pressure liquid chromatography. 12-Lipoxygenase protein was estimated by Western blot using anti-serum against recombinant human platelettype 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.