ANALYSIS OF THE PROTEOME IN HUMAN PITUITARY TUMORS

描述：(改编自申请者的摘要)人类脑下垂体蛋白质组 包括在给定时间内表达的所有蛋白质。与基因组不同， 蛋白质组不是固定的，但它会随着条件的不同而变化。蛋白质组 科学(蛋白质组学)采用最先进的分离技术相结合 蛋白质组研究的技术、质谱学和生物信息学。一个 蛋白质组学研究在生物医学领域的应用前景广阔。 肿瘤病理学研究。中国经济的质与量的变化 与肿瘤形成相关的蛋白质组可以通过一种 健康(对照)与肿瘤组织的比较，以及感兴趣的蛋白质 在这里，蛋白质组学的方法将应用于 人垂体大腺瘤(激素沉默)的蛋白质组研究 肿瘤)。拟议的研究方案的目标是产生一个 人垂体蛋白的二维参考图，并对其进行了表征 在垂体大腺瘤中表达被修饰的蛋白。 蛋白质将通过双向凝胶电泳法分离，并 2D地图将被数字化。对照和肿瘤蛋白质组的二维凝胶图像 将被比较，蛋白质斑点将被量化。它的蛋白质 脑垂体瘤的丰度改变将被识别和描述。 感兴趣的蛋白质将被消化，由此产生的大量 多肽将通过基质辅助激光解吸/电离进行测量 飞行时间质谱仪。这些多肽的氨基酸序列将是 用电喷雾-离子陷阱质谱仪测定。使用这些 多肽图谱和/或测序数据，蛋白质将通过 搜索蛋白质序列数据库。差分式的刻画 表达的脑下垂体蛋白还将包括对 翻译后蛋白质修饰的变化。此外，还有一些 来自对照垂体蛋白质组的突出蛋白质也将是 人类脑下垂体的2D参考数据库将被 建造的。 了解垂体大腺瘤蛋白表达的变化将 有助于阐明大腺瘤形成的基本机制，这可能导致 以开发更有效的手段来治疗和管理这些肿瘤。

DESCRIPTION: (Adapted from applicant's abstract) The human pituitary proteome includes all proteins that are expressed in the given time. Unlike a genome, the proteome is not fixed, but it changes depending on the conditions. Proteome science (proteomics) employs a combination of state-of-the-art separation techniques, mass spectrometry, and bioinformatics for the study of proteomes. A promising prospect is the application of proteome research for the investigation of tumor pathologies. Qualitative and quantitative changes in the proteome that are associated with tumor formation can be monitored by a comparison of healthy (control) vs. tumor tissue, and the proteins of interest can be characterized, Here, the proteomics approach will be applied to the study of the proteome in human pituitary macroadenomas (hormonally silent tumors). The objective of the proposed research program is to generate a two-dimensional reference map of human pituitary proteins, and to characterize the proteins whose expression is modified in pituitary macroadenomas. The proteins will be separated by two-dimensional gel electrophoresis, and the 2D maps will be digitized. 2D gel images from control versus tumor proteomes will be compared, and protein spots will be quantified. The proteins whose abundance is altered in pituitary tumors will be identified and characterized. The protein of interest will be digested, and the masses of the resulting peptides will be measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Amino acid sequence of the peptides will be determined by electrospray-ion trap mass spectrometry. Using these peptide-mapping and/or sequencing data, the protein will be identified by searching a protein sequence database. Characterization of differentially expressed pituitary proteins will also include a detailed investigation of changes in posttranslational protein modifications. In addition, a number of prominent proteins from the control pituitary proteome will also be characterized, and a 2D reference database of the human pituitary will be constructed. Knowledge of the changes in protein expression in pituitary macroadenomas will help clarify fundamental mechanisms of macroadenoma formation, which may lead to the development of more effective means to treat and manage these tumors.