TRANSFORMATION RELATED GENES IN ORAL CANCERS

口腔癌中的转化相关基因

• 批准号: 2688160
• 负责人: David D. Chang
• 金额: $ 10.47万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2688160
• 关键词: cell growth regulation; gene expression; genetic library; molecular cloning; neoplastic transformation; oral pharyngeal neoplasm; representational difference analysis; tissue /cell culture

DESCRIPTION: (adapted from the investigator's abstract) The ability to identify the gene expression differences that can account for phenotypic changes would greatly advanced our current understanding of several important biological events, including development, differentiation, transformation, and senescence. A long-term goal of this proposal is to study the gene expression differences between transformed cells and their normal counterparts. There are two outstanding issues in differential gene expression analysis. First, there is a need for methods that allow identification of a large cohort of differentially expressed genes. Second, as the differential cloning methods improve, there is a need for a mechanism that allows functional analysis of a large number of genes. In Specific Aim 1, they will concentrate on identification of differentially expressed genes, using an in vitro oral carcinogenesis model that allows independent examination of both the early and late events of oncogenic transformation. Representational difference analysis (RDA) will be improved so that a sufficiently large fraction of the gene expression differences between transformed cells and their normal counterparts can be cloned. cDNA array hybridization will be used to establish the expression profile of the cloned differentially expressed genes in other cancer cells. In Specific Aim 2, they will employ an expression cloning strategy to detect genes that can alter growth properties. The output of RDA will be used to construct an eukaryotic expression library. The complexity of such a library, compared to a standard cDNA expression library, is expected to be low and will favor the success of expression cloning. The expression cloning strategy, if successful, will significantly alter the overall approach toward differential gene expression analysis. It is certain that this investigation will lead to the development of many valuable reagents and methods for additional studies in molecular mechanisms of human epithelial cell carcinogenesis and other complex biological events.

描述：(改编自调查员的摘要)能够 确定可解释表型的基因表达差异 变化将极大地促进我们目前对以下几个问题的理解 重要的生物事件，包括发育、分化、 蜕变和衰老。这项提议的一个长期目标是 研究转化细胞与非转化细胞基因表达的差异 正常的对应物。差异基因研究有两个突出问题 表情分析。首先，需要一些方法来允许 鉴定大量差异表达基因。第二, 随着差异克隆方法的改进，需要一种机制 这使得对大量基因进行功能分析成为可能。以特定的目标 1，他们将专注于鉴定差异表达的 基因，使用体外口腔致癌模型，允许独立 对致癌转化的早期和晚期事件进行检查。 代表性差异分析(RDA)将得到改进，以便 足够大的比例的基因表达差异 转化的细胞和它们的正常对应细胞可以被克隆。基因芯片 将使用杂交的方法建立克隆的表达谱 在其他癌细胞中差异表达的基因。在具体目标2中， 他们将使用一种表达克隆策略来检测可以 改变生长特性。RDA的输出将用于构建 真核表达文库。与这样一个库的复杂性相比， 到一个标准的cdna表达文库，预计会很低，并会青睐 表达克隆的成功。表达克隆策略，如果 成功，将显著改变总体方法，以实现 差异基因表达分析。可以肯定的是，这是 调查将导致许多有价值的试剂和 人上皮细胞分子机制的进一步研究方法 细胞癌变和其他复杂的生物学事件。