INVESTIGATING THE SPATIAL BINDING OF CADMIUM AND NICKEL ON THE ESTROGEN RECEPTOR

研究镉和镍对雌激素受体的空间结合

• 批准号: 8170196
• 负责人: Maggie C Louie
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170196
• 关键词: Binding; Cadmium; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Estrogen Receptors; Estrogen receptor positive; Estrogens; Funding; Grant; Heavy Metals; Institution; Location; Malignant Neoplasms; Mammary gland; Metals; Microscopy; Nickel; Receptor Activation; Receptor Signaling; Research; Research Personnel; Resources; Roentgen Rays; Signal Pathway; Source; Structure; United States; United States National Institutes of Health; Woman; absorption; carcinogenesis; in vivo; malignant breast neoplasm; transmission process

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. Breast cancer, one most common cancer that occurs in women in the United States, often develops as estrogen receptor (ER) positive. The progression of ER positive breast cancer is highly dependent on estrogenic stimulation. Recent studies have suggested that heavy metals may contribute to the development of breast cancer by mimicking estrogen?s effect. Often referred to as metalloestrogens, metals like cadmium and nickel have been shown to activate the ER signaling pathway and contribute to mammary gland carcinogenesis. Data from my lab and others have suggested that the actions of cadmium and nickel are ER dependent and multiple studies have demonstrated that the cadmium binds to the estrogen receptor; however, the location of binding remains controversial and requires further analysis. In order to dissect the mechanism of ER activation by cadmium and nickel, we propose to identify the metal interaction domain on the estrogen receptor with the following specific aims: 1) Identify the neighboring atoms involved in the coordination of cadmium and nickel in estrogen receptor using EXAFS (Extended X-ray Absorption Fine Structure), and 2) Identify the metal-ER complex in vivo using microprobe and transmission x-ray microscopy (TXM) in conjunction with fluorescent microscopy.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 乳腺癌是美国女性最常见的癌症，通常以雌激素受体（ER）阳性发展。 ER阳性乳腺癌的进展高度依赖于雌激素刺激。最近的研究表明，重金属可能通过模仿雌激素的作用来有助于乳腺癌的发展。镉和镍等金属通常被称为冶金雌激素，已被证明可以激活ER信号通路并有助于乳腺癌发生。我实验室和其他人的数据表明，镉和镍的作用是依赖性的，多次研究表明，镉与雌激素受体结合。但是，结合的位置仍然存在争议，需要进一步分析。为了通过镉和镍解剖ER激活的机制，我们建议以以下特定目的确定雌激素受体上的金属相互作用结构域：1）确定使用EXAFS使用Exafs（exted X射线吸收式摄像机）的雌激素受体协调的相邻原子，以及使用X射线吸收式摄像机（以及2）viv Indile x-Ray iriper（2）viv Indile x-Ray iriper（2）。 （TXM）与荧光显微镜结合。