ROLE OF LIPIDS IN BREAST CANCER

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 前列腺素HS-2在人乳腺肿瘤中的过度表达无表情 在正常人乳腺组织中观察到PGHS-2的表达。这个 表皮生长因子受体和癌基因erb-2在乳腺中发挥重要作用 癌症。因为SHE细胞代表了一种研究 脂类与EGFR信号通路的相互作用 研究了erb-2的存在如何改变脂代谢。 我们用质粒dna载体转染人成纤维细胞。 含有逆转录病毒v-erbB癌基因或其细胞同源基因 C-erbB-2，建立了稳定的转染系。 转ErbB基因的细胞脂氧合酶活性升高 亚油酸和花生四烯酸的代谢。我们有 研究了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-erbB2/HER2和雌激素受体的表达。 我们观察到高水平的 C-erb B-2和EGF受体表达与亚油酸程度的关系 这些细胞中的酸代谢。脂氧合酶抑制 代谢抑制erbB-2/EGFR细胞DNA合成 人类乳腺细胞中的途径以及脂代谢产物如何改变 依赖于EGFR的磷酸化事件。

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 tumors. No expression of PGHS-2 was observed in normal human breast tissue. The EGFR and the oncogene erb-2 play and important role in breast cancer. Since SHE cells represent a model system for studying the interactions 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 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 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-erbB2/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 pathaway in human breast cells and how lipid metabolites can alter EGFR-dependent phosphorylation events.