ROLE OF LIPIDS IN BREAST CANCER

工作总结：有证据表明，脂质代谢物可能起到 在乳腺癌中的作用。一些数据支持亚油酸的作用 新陈代谢，而其他更新的数据表明过度表达 人体内的PGHS-2 乳房肿瘤。正常人乳腺组织中未见PGHS-2的表达 组织。EGFR和癌基因erb-2在乳腺癌中起重要作用 乳腺癌。因为SHE细胞代表了一种研究 脂质与EGFR信号通路的相互作用我们研究了 ERB-2的存在会改变脂质代谢。我们把正常的 含逆转录病毒-erbB基因DNA载体的SHE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 研究了亚油酸和花生四烯酸在多种植物中的代谢。 不同表达EGF的人乳腺癌细胞株 受体、c-erbB-2/HER2和雌激素受体。我们观察到了一个收盘 C-erbB-2高表达与EGF受体表达的关系 以及这些细胞中亚油酸代谢的程度。抑制 脂氧合酶代谢抑制erbB-2/EGFR细胞DNA合成 过度表达的细胞。我们目前正在研究EGFR信号 人类乳腺细胞中的途径以及脂类代谢物如何改变EGFR- 依赖的磷酸化事件。

Summary of Work: Evidence indicates that lipid metabolites may play a role in breast cancer. Some data support a role for linoleic acid metabolism while other more recent data indicate the over-expression of PGHS-2 in human breast tumor. No expression of PGHS-2 was observed in normal human breast tissue. The EGFR and the oncogenes erb-2 play an important role in breast cancer. Since SHE cells represent a model system for studying the interaction of lipids with the EGFR signaling pathway we examined how the presence of erb-2 would alter lipid metabolism. We transfected normal SHE fibroblasts with plasmid DNA vectors containing the retroviralv-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 examined 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. We are currently examining the EGFR signaling pathway in human breast cells and how lipids metabolites can alter EGFR- dependent phosphorylation events.