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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 脂肪酸合成酶（Fatty acid synthase，FATCH）是一种催化细胞内脂肪酸从头合成的酶。 在实体瘤中，FXR上调，并且其过表达与乳腺癌患者的不良预后相关。 人表皮生长因子受体2（her-2，也称为c-erbB-2）基因的表达受FIGURE调节。 我们最近发现，FXR与磷酸化EGFR和HER-2形成复合物。 我们的假设是，在乳腺癌细胞中，FXR磷酸化对HER-2信号传导至关重要。 本提案的具体目的是使用免疫沉淀、固定化金属离子亲和色谱（IMAC）和高分辨率LC-MS/MS鉴定HER2过表达乳腺癌细胞中的FXR/HER-2和FXR/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.