Development of An In vivo Metastasis Screen

描述（由申请人提供）：工具和资源现在可用于筛选增强体内转移的基因。这些筛选将为药物开发确定新的靶点，这些靶点可以补充目前正在开发或临床使用的疗法。此外，这种筛选提供的信息将有助于减少通过微阵列研究确定的潜在靶点的数量，从而表明哪些基因产物可能驱动转移。我们建议将联合收割机高通量基因表达和抑制技术与体内转移方法学相结合，以加速高达50倍的体内筛选。筛选将指示蛋白质对原发性肿瘤生长、内渗和肺定殖步骤的贡献。第一个目标将集中在生产表达或抑制选定蛋白质的细胞库。第二个目标将评估用于测量池中的构建体分布的检测技术。第三个目标是确定要筛选的人才库的适当组成。第四个和第五个目标将进行初步筛选，并验证筛选中确定的候选人。该R21应用将使筛选的发展成为可能并证明可行性;为评估肿瘤细胞恶性肿瘤最关键特征-转移能力的基因功能提供范例。 评估：

DESCRIPTION (provided by applicant): The tools and resources are now available for the development of screens for genes that enhance metastasis in vivo. Such screens will identify new targets for drug development that may complement therapies currently under development or in clinical use. In addition, the information provided by such screens will aid in reducing the number of potential targets that are identified through microarray studies by indicating which gene products are likely to be driving metastasis. We propose to combine high throughput gene expression and suppression technologies with in vivo metastasis methodology to accelerate in vivo screening by a factor of up to 50. The screen will indicate the contributions of proteins to the steps of primary tumor growth, intravasation, and lung colonization. The first aim will focus on production of pools of cells expressing or suppressing selected proteins. The second aim will evaluate detection technologies for measuring construct distributions in a pool. The third aim will determine the appropriate formation of pools to be screened. The fourth and fifth aims will perform an initial screen and validate candidates identified in the screen. This R21 application will enable the development of the screen and demonstrate feasibility; providing a paradigm for evaluating gene function for the most critical feature of tumor cell malignancy - the ability to metastasize. ASSESSMENT: