ARACHIDONIC ACID AND LINOLEIC ACID METABOLISM IN CELL PROLIFERATION

我们研究了对生长因子（EGF、FGF和PGDF）的反应， 观察到叙利亚仓鼠胚胎细胞FGF的脂质代谢， 刺激PGHS-2的表达和有丝分裂。 FGF没有增强 亚油酸代谢为13-HODE。 一些数据表明， 拟南芥素参与FGF依赖的有丝分裂，但完全参与FGF依赖的有丝分裂。 缺乏证据。 EGF依赖的有丝分裂被抑制， 脂氧合酶抑制剂，但不减弱PGHS抑制剂。 EGF的作用 不刺激前列腺素的形成，但刺激新陈代谢 将亚油酸转化为13-HODE。 13-HODE的形成受到以下因素的调节： EGF受体的酪氨酸激酶活性，但其机制是 不太了解。 我们使用GG-MS技术来测量 内源性13-HODE。 13-在足够浓度下检测到HODE 以增强EGF依赖的有丝分裂。 亚油酸代谢产物 在supB+ SHE细胞中增强EGF依赖的有丝分裂，但在 supB-。 我们还研究了结构特征 增强EGF的细胞分裂作用。 我们已经转染了正常的SHE 用含有逆转录病毒v-erbB的质粒DNA载体的成纤维细胞 癌基因或其细胞同源物c-erbB-2，并建立了稳定的 转染细胞系。erbB-转染的细胞表现出增加的 脂肪氧合酶代谢亚油酸和花生四烯酸。 我们有 开始研究亚油酸和花生四烯酸的代谢， 多种人乳腺癌细胞系，其在其 EGF受体、c-erbB-2/HER 2和雌激素受体的表达。 我们 已经观察到高水平的c-erbB-2和EGF之间的密切联系， 受体表达和亚油酸代谢的程度，在这些 细胞 抑制脂氧合酶代谢减弱DNA合成 在erbB-2/EGFR过表达细胞中。

We have studied the response to growth factors (EGF, FGF and PGDF) and lipid metabolism in Syrian hamster embryo cell FGF was observed to stimulate the expression of PGHS-2 and mitogenesis. FGF did not enhance the metabolism of linoleic acid to 13-HODE. Some data suggest that prostaglandins were involved in FGF dependent mitogenesis but complete evidence is lacking. EGF-dependent mitogenesis was inhibited by lipoxygenase inhibitors but not attenuated by PGHS inhibitors. EGF did not stimulate prostaglandin formation but did stimulate the metabolism of linoleic acid to 13-HODE. The formation of 13-HODE is regulated by the tyrosine kinase activity of the EGF receptor but the mechanism is poorly understood. We used GG-MS techniques to measure the formation of endogenous 13-HODE. 13-HODE was detected in sufficient concentrations to enhance EGF-dependent mitogenesis. The linoleic acid metabolites potentiated EGF-dependent mitogenesis in the supB+ SHE cells but not in the supB-. We have also examined the structural characteristics necessary for enhancing EGF mitogenesis. We have transfected normal SHE fibroblasts with plasmid DNA vectors containing the retroviral v-erbB oncogene or its cellular homolog c-erbB-2 and established stable transfected cell lines. erbB-Transfected cells demonstrate increased lipoxygenase metabolism of both linoleic and arachidonic acid. We have started to examine the metabolism of linoleic and arachidonic acid in a variety of human breast carcinoma cell lines which vary in their expression of EGF receptor, c-erbB-2/HER2, and estrogen receptor. We have observed a close association between high levels of c-erbB-2 and EGF receptor expression and the extent of linoleic acid metabolism in these cells. Inhibition of lipoxygenase metabolism attenuates DNA synthesis in the erbB-2/EGFR overexpressing cells.