POLYOMA HOST INTERACTIONS LEADING TO TUMOR DEVELOPMENT

描述：(改编自调查人员摘要)：我们建议使用 多瘤病毒-小鼠系统研究病毒-宿主相互作用的各个方面 导致肿瘤的诱发。与生物学普遍相关的两个领域 将对癌症的风险进行调查。第一个问题是，显然没有能力 多瘤病毒阻断P53的作用，引发了人们对其作用的质疑 基因组不稳定性在这个系统中驱动肿瘤的发展。这将是 用分子细胞遗传学技术研究白纹伊蚊基因组变化的探讨 多瘤诱导的小鼠肿瘤，研究在组织培养中确定 病毒可覆盖或绕过P53，并衍生表达P53的转基因小鼠 可调节的多瘤T(肿瘤)抗原。第二个领域涉及到 决定易感和易感模式的宿主遗传背景 对肿瘤的抗药性。三个小鼠品系表现出不同的肿瘤反应 将进行研究-1)基于失败而导致肿瘤诱导的敏感性 发展肿瘤免疫，2)对乳腺肿瘤的组织特异性抵抗力，以及3) 骨肿瘤转移到肺部的倾向。遗传学和生理学 我们将使用各种方法来尝试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.