INDUCIBLE MOUSE MODELS FOR SKIN AND HEAD AND NECK CANCER

皮肤癌和头颈癌的诱导小鼠模型

• 批准号: 6955050
• 负责人: Dennis Roop
• 金额: $ 80.26万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6955050
• 关键词: clinical research; cooperative study; disease /disorder model; head /neck neoplasm; human subject; laboratory mouse; microarray technology; model design /development; neoplasm /cancer genetics; neoplastic process; skin neoplasms

DESCRIPTION (provided by applicant): The overall objective of this project is the generation of inducible mouse models that closely mimic the development of human skin and head and neck cancers. My colleagues and I have recently developed inducible mouse models that allow the activation of oncogenes or inactivation of tumor suppressor genes in a restricted area of the skin, oral cavity or esophagus in stem cells that renew these stratified epithelia. Thus, we can create mice with discrete genetic changes in somatic cells that are identical to events that are thought to occur in human tumors. The genetic changes identified to date are primarily associated with early stages of tumor development. Much less is known about genetic changes that occur as tumors progress to metastatic lesions. Thus, our application will focus on recently discovered candidate genes implicated in promoting tumor progression through mechanisms that are both dependent on and independent of genomic instability. To identify novel genetic changes associated with tumor progression in our inducible mouse models, we will analyze tumors using both Affymetrix arrays and BAC/CGH arrays. In parallel studies, we will also analyze human skin and head and neck tumors which exhibit an aggressive nature and propensity to metastasize by Affymetrix arrays and BAC/CGH arrays and compare these findings with results obtained from analysis of the mouse tumors. Our inducible mouse models develop tumors as the result of discrete genetic changes, therefore these models are ideally suited to test novel drugs designed to interfere with specific gene products or signaling pathways. Pilot experiments will be performed to assess the utility of these models as tools for translational studies. Imaging will be utilized for the early detection of metastatic lesions in these studies and to monitor regression following treatment.

描述（由申请人提供）： 该项目的总体目标是生成高度模仿人类皮肤癌和头颈癌发展的诱导小鼠模型。我和我的同事最近开发了诱导型小鼠模型，该模型允许在皮肤、口腔或食道的干细胞的限制区域中激活癌基因或抑癌基因失活，从而更新这些复层上皮。因此，我们可以创造出体细胞中具有离散遗传变化的小鼠，这些变化与被认为发生在人类肿瘤中的事件相同。 迄今为止发现的基因变化主要与肿瘤发展的早期阶段有关。人们对肿瘤进展为转移性病变时发生的基因变化知之甚少。因此，我们的应用将重点关注最近发现的候选基因，这些候选基因通过依赖和独立于基因组不稳定性的机制促进肿瘤进展。 为了在我们的诱导小鼠模型中识别与肿瘤进展相关的新的遗传变化，我们将使用 Affymetrix 阵列和 BAC/CGH 阵列分析肿瘤。在并行研究中，我们还将通过 Affymetrix 阵列和 BAC/CGH 阵列分析表现出侵袭性和转移倾向的人类皮肤和头颈肿瘤，并将这些发现与小鼠肿瘤分析获得的结果进行比较。 我们的诱导小鼠模型由于离散的遗传变化而产生肿瘤，因此这些模型非常适合测试旨在干扰特定基因产物或信号通路的新药物。将进行试点实验以评估这些模型作为转化研究工具的效用。在这些研究中，成像将用于早期检测转移性病变并监测治疗后的消退。