ARACHIDONIC ACID AND LINOLEIC ACID METABOLISM IN CELL PROLIFERATION

我们研究了对生长因子(EGF、FGF和PGDF)的反应以及 观察叙利亚仓鼠胚胎细胞成纤维细胞生长因子的脂代谢 刺激PGHS-2的表达和有丝分裂。成纤维细胞生长因子没有增强 亚油酸代谢为13-HODE。一些数据表明， 前列腺素参与成纤维细胞生长因子依赖的有丝分裂，但完全 证据不足。依赖EGF的有丝分裂生成被抑制 脂氧合酶抑制剂，但不能被PGHS抑制剂减弱。EGF做到了 不会刺激前列腺素的形成，但会刺激新陈代谢 将亚油酸转化为13-HODE。13-HODE的形成受 EGF受体的酪氨酸激酶活性，但其机制是 人们对此知之甚少。我们使用GG-MS技术来测量 内源性13-HODE。在足够的浓度下检测到13-HODE 以增强EGF依赖的有丝分裂形成。亚油酸代谢物 增强SuB+SHE细胞中EGF依赖的有丝分裂，而不是 超级市场B-。我们还研究了结构特征 是促进EGF有丝分裂所必需的。我们已经将正常的SHE 含逆转录病毒v-erbB的DNA载体的成纤维细胞 癌基因或其细胞同系物c-erb B-2并建立稳定 转染型细胞系。转ErbB基因的细胞数量增加 亚油酸和花生四烯酸的脂氧合酶代谢。我们有 开始研究亚油酸和花生四烯酸在 不同类型的人乳腺癌细胞系 表皮生长因子受体、c-erbB-2/HER2和雌激素受体的表达。我们 观察到高水平的c-erbB-2和EGF之间有密切的联系 受体的表达和亚油酸代谢的程度 细胞。抑制脂氧合酶代谢可减弱DNA合成 在erbB-2/EGFR高表达细胞中表达。

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.