Tumor Host Range Mutants of Polyoma and Their Targets

多瘤的肿瘤宿主范围突变体及其靶标

• 批准号: 6946339
• 负责人: THOMAS Livingston BENJAMIN
• 金额: $ 60.51万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946339
• 关键词: DNA replication; Polyomavirus muris 1; host neoplasm interaction; host organism interaction; mutant; neoplasm /cancer genetics; ovary neoplasms; tissue /cell culture; tumor suppressor genes; viral carcinogenesis; virus DNA; virus antigen; virus genetics; virus infection mechanism; virus related neoplasm /cancer; virus replication; yeast two hybrid system

DESCRIPTION (provided by the applicant): This project concerns the use of a 'tumor host range' (T-HR) selection procedure for isolation of host range mutants of Polyoma virus. The procedure involves screening and selection of virus mutants for their ability to grow on non-polyoma transformed or tumor-derived cells and inability to grow in normal primary mouse cells. The procedure is coupled to the yeast two hybrid system using wild type virus T antigen sequences as bait to screen mouse embryo cDNA libraries. Absence of interaction of target cDNAs with the mutant bait is taken as an indication of a physiologically relevant target in virus replication or transformation. The procedure is viewed as a possible way to uncover new tumor suppressor genes or other factors with which the virus must interact in normal cells in order to grow and which are altered or missing in cancer cells. We will use results from a partially characterized T-HR mutant and its putative tumor suppressor gene target to produce a mouse model of ovarian carcinoma.

描述（由申请人提供）：该项目涉及使用一个 用于分离宿主范围的“肿瘤宿主范围”（T-HR）选择程序 多瘤病毒的突变体。该程序包括筛选和选择 病毒突变体在非多瘤转化的或 肿瘤来源的细胞和不能在正常的原代小鼠细胞中生长。的 程序偶联到酵母双杂交系统使用野生型病毒T 抗原序列作为诱饵筛选小鼠胚胎cDNA文库。没有 靶cDNA与突变体诱饵的相互作用被认为是突变体诱饵与靶cDNA相互作用的指示。 在病毒复制或转化中的生理学相关靶点。的 这一过程被认为是发现新的肿瘤抑制基因的一种可能方法， 病毒在正常细胞中必须与之相互作用以 在癌细胞中发生改变或缺失。我们将使用来自 一个部分特征性的T-HR突变体及其推定的肿瘤抑制基因 以产生卵巢癌小鼠模型。