FATTY ACID SYNTHASE AND EGFR/HER2 CROSS-TALK IN BREAST CANCER CELLS

乳腺癌细胞中脂肪酸合酶和 EGFR/HER2 的相互作用

• 批准号: 8365473
• 负责人: FRANCISCO J ESTEVA
• 金额: $ 2.87万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365473
• 关键词: Affinity Chromatography; Biology; Breast Cancer Cell; Cancer Patient; Cells; Complex; ERBB2 gene; Enzymes; Epidermal Growth Factor Receptor; Fatty Acids; Fatty-acid synthase; Funding; Grant; Human; Immunoprecipitation; Ions; Metals; National Center for Research Resources; Phosphorylation; Phosphorylation Site; Principal Investigator; Proteomics; Research; Research Infrastructure; Resolution; Resources; Signal Transduction; Solid Neoplasm; Source; United States National Institutes of Health; cost; malignant breast neoplasm; outcome forecast; overexpression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Fatty acid synthase (FASN) is the enzyme that catalyzes the de novo synthesis of fatty acids in cells. FASN is up-regulated in solid tumors, and its overexpression has been associated with poor prognosis in breast cancer patients. FASN regulates the expression of the human epidermal growth factor receptor 2 (her-2 also known as c-erbB-2) gene. We have recently found that FASN forms a complex with phosphorylated EGFR and HER-2. Our hypothesis is that FASN phosphorylation is critical for HER-2 signaling in breast cancer cells. The specific aim of this proposal is to identify the FASN/HER-2 and FASN/EGFR phosphorylation sites in HER2-overexpressing breast cancer cells using immunoprecipitation, immobilized metal-ion affinity chromatography (IMAC), and high resolution LC-MS/MS.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 脂肪酸合成酶(FASN)是催化细胞内脂肪酸从头合成的酶。FASN在实体瘤中表达上调，其过度表达与乳腺癌患者的预后不良有关。FASN调控人表皮生长因子受体2(HER-2，又称c-erbB-2)基因的表达。我们最近发现FASN与磷酸化的EGFR和HER-2形成一个复合体。我们的假设是，FASN的磷酸化对乳腺癌细胞中的HER-2信号转导至关重要。本研究的具体目的是利用免疫沉淀、固定化金属离子亲和层析和高分辨LC-MS/MS鉴定HER2过表达乳腺癌细胞中的FASN/HER-2和FASN/EGFR磷酸化位点。