Gene Expression in Cancer by Microarray Hybridization

通过微阵列杂交在癌症中进行基因表达

基本信息

批准号：
7230478
负责人：
PATRICK O. BROWN
金额：
$ 43.88万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-09-30 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7230478
关键词：
4-thiouracil Adopted Affect Affinity Chromatography Arabidopsis Architecture Area Basal cell carcinoma Biological Biological Models Cancer Model Cell Proliferation Cells Characteristics Classification Colon Carcinoma Cultured Cells DNA Microarray Chip DNA Microarray format Databases Development Diagnosis Elements Funding Gene Expression Gene Expression Profiling Genes Genome Goals Grant Human Human Cell Line Individual Investigation Kinetics Knowledge Malignant Epithelial Cell Malignant Neoplasms Maps Measurement Messenger RNA Methodology Methods Modeling Molecular Molecular Biology Nature Nuclear Export Pathogenesis Patient Care Patient Care Planning Pattern Phase Physiologic pulse Physiological Postdoctoral Fellow Proteins Pulse taking RNA RNA Decay RNA Splicing RNA chemical synthesis RNA-Binding Proteins Rate Regulation Reproducibility Research Research Personnel Risk Role Role playing therapy Saccharomyces cerevisiae Signal Transduction Source Specificity Students Surveys System Testing Time Tissues Today Tracer Transcript Translational Regulation Translations Variant Work Yeasts analytical tool autocrine base cancer cell cancer microarray cancer stem cell cell type design frontier genome-wide analysis infancy inhibitor/antagonist innovation insight mRNA Decay mRNA Transcript Degradation malignant breast neoplasm new technology outcome forecast paracrine programs research study self-renewal tool

项目摘要

DESCRIPTION (provided by applicant): From the start, the goal of this program has been the development and application of genome-wide approaches to systematic and quantitative analysis of gene expression patterns in cancer. In the eight years since we began this project, the experimental and analytical tools for systematic studies of global gene expression patterns at the level of transcript abundance have developed dramatically and they have become widely available and widely used for the study of cancer. The resulting studies have produced a wealth of new insight into cancer and they are even beginning to influence patient care. Profiling mRNA transcript levels, however, provides only a partial picture of the global gene expression program. While there is abundant evidence that regulation of the translation, subcellular localization and decay of mRNA are critical elements of biological regulation, practical and robust genome-wide approaches to studying these levels of regulation remain to be developed. As a result, our knowledge of the systems architecture, molecular mechanisms and biological roles of these regulatory mechanisms, including the roles they play in human cancer, is barely in its infancy. We therefore propose to develop practical, robust, high-throughput methods using DNA microarrays to profile three critical aspects of global regulation at the post-transcriptional level: translational regulation, regulation of mRNA degradation, and the specific interactions of RNA binding proteins with their targets. These studies will build on preliminary studies we've already begun in the Saccharomyces cerevisiae model system, but will focus on human cells. As the essential methodologies are developed, we will apply them to developing a foundational framework of knowledge, investigating the patterns in which these regulatory mechanisms are used in basic physiological and developmental programs, how they vary from one cell type to another and between individuals, and beginning to investigate the underlying molecular mechanisms. The goal is to develop both the experimental methodology and an interpretive framework to the point that these post-transcriptional levels of gene expression can be systematically profiled and studied on a genome-wide scale almost as routinely as transcript levels are today.

描述（由申请人提供）：从一开始，该计划的目标就是开发和应用全基因组方法，对癌症中的基因表达模式进行系统和定量分析。自从我们开始这个项目以来的八年里，用于在转录本丰度水平上系统研究全球基因表达模式的实验和分析工具取得了巨大的发展，并且它们已被广泛使用并广泛用于癌症研究。由此产生的研究对癌症产生了丰富的新见解，甚至开始影响患者的护理。然而，分析 mRNA 转录水平只能提供全局基因表达程序的部分情况。虽然有大量证据表明 mRNA 的翻译调节、亚细胞定位和衰变是生物调节的关键要素，但研究这些调节水平的实用且强大的全基因组方法仍有待开发。因此，我们对这些调节机制的系统架构、分子机制和生物学作用（包括它们在人类癌症中发挥的作用）的了解还处于起步阶段。因此，我们建议开发实用、稳健、高通量的方法，利用 DNA 微阵列来分析转录后水平全局调控的三个关键方面：翻译调控、mRNA 降解调控以及 RNA 结合蛋白与其靶标的特异性相互作用。这些研究将建立在我们已经在酿酒酵母模型系统中开始的初步研究的基础上，但将重点关注人类细胞。随着基本方法的开发，我们将应用它们来开发基础知识框架，研究这些调节机制在基本生理和发育程序中使用的模式，它们如何从一种细胞类型到另一种细胞类型以及个体之间的差异，以及开始研究潜在的分子机制。我们的目标是开发实验方法和解释框架，使这些基因表达的转录后水平可以像今天的转录水平一样在全基因组范围内系统地进行分析和研究。