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EVALUATION OF DOMINANTLY-ACTING RAS ONCOGENES

对起主导作用的 RAS 癌基因的评估

基本信息

批准号：
6459503
负责人：
ERIC J. STANBRIDGE
金额：
$ 7.52万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-05-01 至 2002-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6459503
关键词：
alleles antisense nucleic acid bladder neoplasm carcinogenesis colon neoplasms fibrosarcoma gene mutation gene targeting heterozygote laboratory mouse neoplasm /cancer genetics oligonucleotides pancreas neoplasms protooncogene

项目摘要

DESCRIPTION: The aim of this proposal is to determine whether maintenance of the human cancer cell tumorigenic phenotype depends on the continued presence of activated ras oncogenes. Three different experimental protocols are proposed: 1) activated ras alleles will be inactivated by targeted homologous recombination, or by the expression of a doubly mutant ras dominant negative allele; 2) dominant negative alleles of proteins in the 2 well characterized ras signalling pathways will be used to selectively disrupt each pathway; and 3) ras antisense oligonucleotides will be used to modify the in vitro growth properties and tumorigenic potential of human tumor cells containing activated ras alleles. The human tumor cells used for these experiments are heterozygous for activating mutations in H-, K- or N-ras. Assays of genetically modified or oligonucleotide-treated cells will include biochemical examination of ras and ras-dependent signalling pathways, growth and morphology in vitro, and tumor formation in mice.

说明：本提案的目的是确定维护是否人类癌细胞致瘤表型的持续变化取决于存在激活的ras癌基因。三种不同的实验提出了以下方案：1）激活的ras等位基因将被灭活，靶向同源重组，或通过表达双突变ras显性负等位基因; 2）显性负等位基因在2个良好表征的ras信号通路中的蛋白质将被用于选择性地破坏每种途径;和3）ras反义寡核苷酸将用于改变体外生长特性含活化ras的人肿瘤细胞的致瘤潜能等位基因。用于这些实验的人类肿瘤细胞是 H-、K-或N-ras中激活突变的杂合子。的测定经遗传修饰或经利格列汀处理的细胞将包括 ras和ras依赖性信号通路的生化检查，体外生长和形态以及小鼠肿瘤形成。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Direct evidence for the contribution of activated N-ras and K-ras oncogenes to increased intrinsic radiation resistance in human tumor cell lines.

DOI：
发表时间：
2000-12
期刊：
Cancer research
影响因子：
11.2
作者：
E. Bernhard;E. Stanbridge;Swati Gupta;Anjali K. Gupta;Daniel Soto;V. Bakanauskas;G. Cerniglia;R. Muschel;W. Mckenna
通讯作者：
E. Bernhard;E. Stanbridge;Swati Gupta;Anjali K. Gupta;Daniel Soto;V. Bakanauskas;G. Cerniglia;R. Muschel;W. Mckenna

Paired human fibrosarcoma cell lines that possess or lack endogenous mutant N-ras alleles as experimental model for Ras signaling pathways.

具有或缺乏内源突变 N-ras 等位基因的配对人类纤维肉瘤细胞系作为 Ras 信号通路的实验模型。