Modulation of epidermal tumor development caused by targeted overexpression of epidermis-type 12S-lipoxygenase.
نویسندگان
چکیده
In contrast to other 12S-lipoxygenase (LOX) isoforms expressed in the skin of mice, epidermis-type (e) 12S-LOX was found to be transcriptionally down-regulated in the course of epidermal tumor development in NMRI mice. This may indicate that this enzyme is related to antitumorigenic rather than protumorigenic effects. To test this hypothesis, two transgenic mouse lines were generated that differentially expressed e12S-LOX under the control of the bovine keratin 6 promoter known to be constitutively up-regulated in mouse skin tumors. As compared with the wild-type, low transgene expression correlated with a decreased skin tumor response paralleled by an up-regulation of leukocyte-type 12S-LOX and an accumulation of the linoleic acid derivative 13S-hydroxyoctadecadienoic acid. In contrast, high transgene expression coincided with an increased tumor response paralleled by a strong keratin 6 promoter-driven up-regulation of the transgenic e12S-LOX and an accumulation of the arachidonic acid derivative 12S-hydroxyeicosatetraenoic acid as the predominant LOX product. These results indicate a complex interaction between different LOX isoforms and an opposite role of arachidonic acid and linoleic acid products in the modulation of skin carcinogenesis.
منابع مشابه
Positional- and stereo-selectivity of fatty acid oxygenation catalysed by mouse (12S)-lipoxygenase isoenzymes.
A quantitative stereochemical analysis of the products generated by recombinant mouse (12S)-lipoxygenase isoenzymes was performed with arachidonic acid and linoleic acid as substrates. The leucocyte-type (12S)-lipoxygenase generated, in addition to 12-hydroxyeicosatetraenoic acid (12-HETE) as the main product, 15- and 8-HETE from arachidonic acid and 13- and 9-hydroxyoctadecadienoic acid (13- a...
متن کاملImaging features of estrogen-negative breast cancers: a correlation study with human epidermal growth factor type II overexpression
Background: Estrogen-negative breast cancers have different clinical course, prognostic features and treatment response in comparison to estrogen receptor-positive (ER-positive) breast cancers. Human epidermal growth factor receptor 2 (HER2) oncoprotein has found to have a pivotal role in natural cell growth and cell division and is suggested to be directly related to tumor invasiveness in brea...
متن کاملCPK3-phosphorylated RhoGDI1 is essential in the development of Arabidopsis seedlings and leaf epidermal cells
The regulation of Rho of plants (ROP) in morphogenesis of leaf epidermal cells has been well studied, but the roles concerning regulators of ROPs such as RhoGDIs are poorly understood. This study reports that AtRhoGDI1 (GDI1) acts as a versatile regulator to modulate development of seedlings and leaf pavement cells. In mutant gdi1, leaf pavement cells showed shorter lobes in comparison with tho...
متن کاملArachidonate 12-lipoxygenase of platelet-type in human epidermal cells.
A homogenate of epidermal cells isolated from human skin converted arachidonic acid to 12S-hydroxy-5, 8,10,14-eicosatetraenoic acid and 15-hydroxy-5, 8,11,13-eicosatetraenoic acid as the main lipoxygenase products. The production of these hydroxy acids was not stimulated by the addition of 1 mM NADPH required for cytochrome P-450 reaction, but inhibited by 65-75% with 40 microM nordihydroguaiar...
متن کاملEpidermal growth factor enhances a microsomal 12-lipoxygenase activity in A431 cells.
12-Hydroxyeicosatetraenoic acid (12-HETE) is formed from arachidonic acid either by 12-lipoxygenase or by a cytochrome P450 monooxygenase. 12-Lipoxygenase is generally localized in the soluble cytosolic fraction, and the cytochrome P450 monooxygenase is a microsomal enzyme. In this study, 12-HETE biosynthesis and the regulation of 12-HETE biosynthesis by epidermal growth factor (EGF) in A431 ce...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer research
دوره 62 16 شماره
صفحات -
تاریخ انتشار 2002