Eling T E, Glasgow W C
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Cancer Metastasis Rev. 1994 Dec;13(3-4):397-410. doi: 10.1007/BF00666106.
In this article we have reviewed and discussed the results of our investigation of lipid metabolites as modulators of epidermal growth factor (EGF) signaling pathways. We have studied epidermal growth factor-dependent mitogenesis in BALB/c 3T3 and Syrian hamster embryo (SHE) cells in culture. We observed that EGF stimulates the formation of prostaglandins in BALB/c 3T3 cells and their formation appears to be necessary for EGF dependent mitogenesis. EGF did not stimulate PGE2 formation in SHE cells and in fact, exogenously added PGE2 inhibited mitogenesis. In both cell lines, EGF stimulated the formation of lipoxygenase-derived 13(S)-hydroxyoctadecadienoic acid (13-HODE) and inhibition of 13-HODE formation attenuated mitogenesis. The addition of 13-(S)-HODE enhanced EGF-dependent mitogenesis but when added alone, the compound was not mitogenic. Other metabolites, including lipoxygenase metabolites of arachidonic acid, were either weak simulators of EGF-dependent mitogenesis or essentially inactive. The 13(S)-HODE appears to be formed by an apparently unique lipoxygenase that is regulated by the tyrosine kinase activity of the EGF receptor. The mechanisms by which lipids, particularly the lipoxygenase-derived linoleic acid metabolites, modulate the EGF signaling pathways leading to cell proliferation is discussed. The possible significance of lipoxygenase and prostaglandin H synthase-dependent metabolism of unsaturated fatty acids in breast and colon cancer is also discussed.
在本文中，我们回顾并讨论了对脂质代谢产物作为表皮生长因子（EGF）信号通路调节剂的研究结果。我们研究了培养的BALB/c 3T3和叙利亚仓鼠胚胎（SHE）细胞中依赖表皮生长因子的有丝分裂。我们观察到，EGF刺激BALB/c 3T3细胞中前列腺素的形成，其形成似乎是EGF依赖性有丝分裂所必需的。EGF并未刺激SHE细胞中PGE2的形成，事实上，外源性添加的PGE2抑制了有丝分裂。在这两种细胞系中，EGF刺激了脂氧合酶衍生的13（S）-羟基十八碳二烯酸（13-HODE）的形成，而抑制13-HODE的形成会减弱有丝分裂。添加13-（S）-HODE可增强EGF依赖性有丝分裂，但单独添加该化合物时并无促有丝分裂作用。其他代谢产物，包括花生四烯酸的脂氧合酶代谢产物，要么是EGF依赖性有丝分裂的弱刺激剂，要么基本无活性。13（S）-HODE似乎由一种明显独特的脂氧合酶形成，该酶受EGF受体酪氨酸激酶活性的调节。本文讨论了脂质，特别是脂氧合酶衍生的亚油酸代谢产物调节导致细胞增殖的EGF信号通路的机制。还讨论了脂氧合酶和前列腺素H合酶依赖性不饱和脂肪酸代谢在乳腺癌和结肠癌中的可能意义。
