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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.