Genetic Analysis of DBC2

描述（由申请人提供）：一个新的基因，DBC 2，最近被分离和初步研究的DBC 2表明，它是一个潜在的候选人的肿瘤抑制。长期目标包括对DBC 2进行遗传分析以验证其作为肿瘤抑制基因;对DBC 2进行功能分析以阐明DBC 2的生理和病理作用;以及对DBC 2的肿瘤生理学研究以提供对乳腺癌和肺癌发展的新见解。我们将利用诱导型基因表达系统在体外测试DBC 2的功能。突变将被引入预测的功能结构域。野生型和突变的DBC 2将被诱导到各种类型的细胞中。将分析表型和表达模式的改变。具体目标2。将研究癌症中DBC 2的转录调控，将在细胞系和原发性肿瘤中研究DBC 2的表达和DBC 2启动子区域的甲基化状态。具体目标3。为进一步研究DBC 2的细胞功能奠定基础。将产生针对DBC 2的抗体，将分析DBC 2在各种组织中的生理表达。具体目标4。我们将使用胚胎干细胞（ES）技术来产生Dbc 2缺陷小鼠模型，并分析这些小鼠的肿瘤易感性。

DESCRIPTION (provided by applicant): A novel gene, DBC2, was recently isolated and preliminary studies of DBC2 indicate that it is a potential candidate for a tumor suppressor. The long-term objectives include genetic analysis of DBC2 to validate it as a tumor suppressor; functional analysis of DBC2 to clarify physiological and pathological roles of DBC2; and studies of tumor physiology of DBC2 to provide new insights to breast and lung cancer development, The goal of this research project is to test the hypothesis that DBC2 is a tumor suppressor gene, Specific aims are: Specific Aim 1. We will utilize inducible gene expression systems to test the DBC2 function in vitro. Mutations will be introduced into predicted functional domains. Wild type and mutated DBC2 will be induced into various types of cells. Alterations of phenotypes and expression patterns will be analyzed. Specific Aim 2. Transcriptional regulation of DBC2 in cancer will be studied, Expression of DBC2 and the methylation status of the DBC2 promoter region will be investigated in cell lines and primary tumors. Specific Aim3. We will lay the foundations for studies on cellular functions of DBC2. Antibodies against DBC2 will be generated, Physiological expression of DBC2 in various tissues will be analyzed. Specific Aim 4. We will use embryonic stem (ES) cell technology to generate a Dbc2-deficient mouse model and analyze these mice for tumor susceptibility.