Fhit Function in Human Cancer

Fhit 在人类癌症中的功能

• 批准号: 6570497
• 负责人: KAY HUEBNER
• 金额: $ 15.13万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570497
• 关键词: Drosophilidae; apoptosis; athymic mouse; binding proteins; cell line; chimeric proteins; esophagus neoplasm; gene expression; gene mutation; genetic mapping; human tissue; lung neoplasms; protein structure function; stomach neoplasms; tumor suppressor proteins; yeast two hybrid system

DESCRIPTION: (Applicant's Description) One or both alleles of the FHIT gene are disrupted in a large fraction of many different types of human tumors. In tumor-derived cell lines and primary tumors with defined FHIT DNA alterations, there is a correlation between DNA alteration, detection of altered RT-PCR products and reduction in the level of Fhit protein. Additionally, replacement of Fhit expression in tumor cell lines suppresses tumorigenicity. This result has been confirmed by recent studies from another laboratory using an adenovirus/Fhit vector. Most recently, immunohistochemical studies of cervical, lung, gastric, bladder, pancreatic and kidney carcinomas have shown that large fractions of these primary tumors express reduced levels or no Fhit protein. This project will continue to study Fhit function by characterizing three possible Fhit, Nit or NitFhit interacting proteins identified from a D. melanogastor library using fly NitFhit as bait in yeast two-hybrid trapping experiments. The candidate interacting proteins are: 1) the c-terminus of the fly coracle protein, a homolog of mammalian 4.1 proteins; 2) a fatty acid binding protein homolog; 3) a fly polypeptide, Dcl5, without known homologs. The interactions will be confirmed in biochemical assays in fly or human systems. Each interaction pathway will then be dissected to understand its role in Fhit signaling. In parallel, Project 1 investigators will participate in characterization of deletions and arrangements of FHIT/FRA3B in specific cancer cells (with Project 2) and will prepare mutant Nit and Fhit proteins in the framework of structural predictions with Project 3.

描述：（申请人的描述）fhit基因的一个或两个等位基因 在许多不同类型的人类肿瘤的大部分中被破坏。在 肿瘤衍生的细胞系和具有定义FHIT DNA改变的原发性肿瘤， DNA改变之间存在相关性，检测改变的RT-PCR 产品和FHIT蛋白水平的降低。此外， 肿瘤细胞系中FHIT表达的替换会抑制肿瘤性。 最新的一项实验室的研究证实了这一结果 腺病毒/FHIT载体。最近，有关免疫组织化学研究 宫颈，肺，胃，膀胱，胰腺和肾癌已显示 这些原发性肿瘤的大部分表达了降低的水平或没有FHIT 蛋白质。该项目将通过表征来继续研究FHIT功能 从D。 黑色素库库使用飞nitfhit作为酵母双杂交诱捕的诱饵 实验。候选蛋白的相互作用是：1） 苍蝇赛蛋白，哺乳动物4.1蛋白的同源物； 2）脂肪酸 结合蛋白质同源物； 3）蝇多肽DCL5，没有已知同源物。 相互作用将在苍蝇或人类的生化测定中得到确认 系统。然后将剖析每个互动途径，以了解其 在FHIT信号中的作用。 同时，项目1调查人员将参与表征 在特定癌细胞中FHIT/FRA3B的缺失和排列（与 项目2）并将在框架内准备突变的NIT和FHIT蛋白 项目3的结构预测。