RASSF1 Tumor Suppressor Gene

RASSF1抑癌基因

• 批准号: 6464188
• 负责人: Gerd P Pfeifer
• 金额: $ 31.15万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6464188
• 关键词: apoptosis; athymic mouse; biological signal transduction; carcinogenesis; cervix neoplasms; chromosome deletion; clinical research; colon neoplasms; gene expression; gene targeting; genetically modified animals; guanine nucleotide binding protein; head /neck neoplasm; human tissue; laboratory mouse; lung neoplasms; neoplasm /cancer genetics; neoplastic growth; ovary neoplasms; prostate neoplasms; protein binding; protein isoforms; renal cell carcinoma; tumor suppressor genes; yeast two hybrid system

DESCRIPTION (provided by applicant): Loss of genetic material from chromosome 3p21.3 is one of the most common and earliest identified events in the pathogenesis of human solid tumors. The chromosomal area 3p2l.3 is thought to harbor at least one important tumor suppressor gene. In preliminary studies, we have identified and cloned a new gene from the common homozygous deletion area at 3p2l.3 and found that this gene is epigenetically inactivated in a large percentage of human lung cancers and breast cancers. The gene, named RASSF1A (Ras Association Domain Family 1A), has homology to the mammalian Ras effector Nore1. Our hypothesis is that RASSF1A is the tumor suppressor gene on 3p21.3. We will define the role of RASSF1A in the pathogenesis of human cancers by searching for aberrations of the gene (primarily epigenetic) in different types of cancer. We will prepare selective mouse knockouts of the two major alternative transcripts originating from the RASSF1 locus, with a focus on RASSF1A, which is inactivated in tumors. We will determine whether mice with heterozygous or homozygous deletions of this gene develop tumors. The homology of the RASSF1A gene with the mammalian Ras effector Nore1 suggests that the gene product may function in signal transduction pathways involving Raslike proteins. We will search for protein binding partners, including downstream targets, by using a series of defined Ras family proteins and yeast two-hybrid screens. The effect of RASSF1 expression on RAS signaling pathways will be studied. We will examine if RASSF1A, alone or in combination with activated RAS, induces cell death (apoptosis).

描述（由申请人提供）：染色体中遗传物质的丧失 3P21.3是最常见和最早确定的事件之一 人实体瘤的发病机理。染色体面积3p2l.3被认为是 至少有一个重要的肿瘤抑制基因。在初步研究中，我们 已经从公共纯合缺失区域鉴定并克隆了一个新基因 在3p2l.3处，发现该基因在大的 人类肺癌和乳腺癌的百分比。该基因，名为rassf1a （RAS协会域家族1A），与哺乳动物RAS效应器具有同源性 Nore1。我们的假设是RASSF1A是3P21.3上的肿瘤抑制基因。 我们将通过 寻找不同类型的基因的像差（主要是表观遗传学） 癌症。我们将准备两个主要的鼠标淘汰赛 源自RASSF1基因座的替代成绩单，重点 RASSF1A，在肿瘤中被灭活。我们将确定是否与 该基因的杂合或纯合缺失会发展出肿瘤。同源性 带有哺乳动物RAS效应子Nore1的RASSF1A基因的表明 基因产物可能在涉及raslike的信号转导途径中起作用 蛋白质。我们将搜索蛋白质约束伴侣，包括下游 目标，使用一系列定义的RAS家族蛋白和酵母双杂交 屏幕。 RASSF1表达对RAS信号通路的影响将是 研究。我们将检查RASSF1A是单独的还是与激活的 RAS，诱导细胞死亡（凋亡）。