ROLE OF LIPIDS IN BREAST CANCER

脂质在乳腺癌中的作用

• 批准号: 6106627
• 负责人: T ELING
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6106627
• 关键词: breast neoplasms; epidermal growth factor; female; fibroblasts; growth factor receptors; human genetic material tag; human tissue; linoleate; lipid metabolism; neoplasm /cancer genetics; phosphoproteins; transfection /expression vector

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.

有证据表明，脂质代谢物可能在 在乳腺癌中的作用一些数据支持亚油酸的作用 而其他最近的数据表明， PGHS-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。的 EGFR和癌基因erb-2在乳腺癌中起重要作用 癌由于SHE细胞代表了用于研究 脂质与EGFR信号通路的相互作用，我们 研究erb-2的存在如何改变脂质代谢。 我们用质粒DNA载体转染正常SHE成纤维细胞， 含有逆转录病毒v-erbB癌基因或其细胞同源物 c-erbB-2基因转染细胞，建立了稳定的转染细胞系。 erbB-转染的细胞显示脂氧合酶增加 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。 我们观察到高水平的 c-erbB-2和EGF受体表达及亚油酸程度 这些细胞中的酸代谢。脂氧合酶抑制 代谢减弱erbB-2/EGFR中的DNA合成 人类乳腺细胞中的通路以及脂质代谢物如何改变 EGFR依赖性磷酸化事件。