POLYOMA HOST INTERACTIONS LEADING TO TUMOR DEVELOPMENT

描述：（改编自研究者摘要）：我们建议使用 多瘤病毒-小鼠系统，用于研究病毒-宿主相互作用方面 导致肿瘤的诱导。两个与生物学相关的领域 癌症将被调查。第一个问题是， 多瘤病毒阻断p53的作用，引起了对多瘤病毒作用的质疑。 基因组的不稳定性在这个系统中驱动肿瘤的发展。这将是 利用分子细胞遗传学技术研究基因组变化， 多瘤诱导的小鼠肿瘤，组织培养研究，以确定如何 病毒可以覆盖或绕过p53，并衍生出表达p53的转基因小鼠。 可调节的多瘤T（肿瘤）抗原。第二个领域涉及以下方面的作用： 确定易感性模式的宿主遗传背景， 抗肿瘤。三种小鼠品系表现出不同的肿瘤反应 1）基于未能对肿瘤诱导的敏感性， 产生肿瘤免疫，2）对乳腺肿瘤的组织特异性抗性，和3） 骨肿瘤转移到肺部的倾向。遗传和生理 方法将被用来试图了解这些主机的基础 表型

DESCRIPTION: (Adapted from the Investigator's abstract): We propose to use the polyoma virus-mouse system to investigate aspects of virus-host interactions leading to induction of tumors. Two areas of general relevance to the biology of cancer will be investigated. The first concerns the apparent inability of polyoma virus to block the actions of p53, raising questions of the role of genomic instability in driving tumor development in this system. This will be approached using molecular cytogenetic techniques to study genomic changes in polyoma-induced mouse tumors, studies in tissue culture to determine how the virus may override or bypass p53, and derivation of transgenic mice expressing regulatable polyoma T (tumor) antigens. The second area concerns the roles of the host genetic background in determining patterns of susceptibility and resistance to tumors. Three mouse strains exhibiting different tumor responses will be studied - 1) susceptibility to tumor induction based on failure to develop tumor immunity, 2) tissue specific resistance to mammary tumors, and 3) propensity of bone tumors to metastasize to the lung. Genetic and physiological approaches will be used in attempts to understand the bases of these host phenotypes.