Modeling Airway Lung Cancer and the Role of Inflammation

描述（由申请人提供）： 肺是一个复杂的器官，其主要功能是允许体液和外部环境之间的气体交换。持续暴露于毒素使肺上皮细胞极易发生致癌转化，导致肺癌的发展。这是由肺癌是美国男女癌症相关死亡的主要原因这一事实所证实的。模拟肺癌的突变小鼠的建立将有助于理解调节这种疾病发展的分子机制，并有助于开发早期检测和治疗这种疾病的方法。在小鼠中建立肺癌模型并不是一项简单的任务。肺癌不是一种独特的疾病，但可分为四种主要的组织学可识别的亚型[eI-Torky，1990 #3]。这些亚型是腺癌、鳞状细胞癌、小细胞癌和大细胞癌。目前，鳞状细胞癌和腺癌是美国最常见的肺癌类型，腺癌是女性最常见的肺癌形式。事实上，腺癌已增加到45%的支气管癌与鳞状细胞癌和大细胞癌下降，而小细胞癌一直保持在20%。该MMHCC应用的目标是通过创建破坏与人类肺癌相关的特定基因或途径的遗传修饰来开发肺腺癌的小鼠模型。这些修饰将针对小鼠气道的一种特定细胞类型，即Clara细胞。一旦这些模型中的癌症进展得到表征，将确定炎症在这些模型中癌症进展中所起的作用。这些模型的分析包括癌症进展期间分子变化的最新成像和DNA和蛋白质组学分析。

DESCRIPTION (provided by applicant): The lung is a complex organ with the primary function of allowing the exchange of gasses between the body fluids and the external environment. The constant exposure to toxins makes the pulmonary epithelial cells highly susceptible to oncogenic transformation, leading to the development of lung cancer. This is borne by the fact that lung cancer is the leading cause of cancer related death in both sexes in the United States. The establishment of mutant mice that mimic the lung cancer will aid in the understanding of the molecular mechanisms regulating the development of this disease as well as aid in the development of means of early detection and the treatment of this disease. Modeling lung cancer in mice is not a simple task. Lung cancer is not one distinct disease but can be divided into four major, histologically identifiable subtypes [eI-Torky, 1990 #3]. These subtypes are adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and large cell carcinoma. Currently, squamous cell carcinoma and adenocarcinoma are the most common type of lung cancer in the United States with adenocarcinoma being the most common form of lung cancer in women. In fact adenocarcinoma has increased to 45% of bronchogenic carcinomas with declines in squamous and large cell carcinomas, while small cell has remained at 20%. The goal of this MMHCC application is to develop mouse models for adenocarcinoma of the lung by creating genetic modifications that disrupt specific genes or pathways that have been associated with human lung cancer. These modifications will be targeted to one specific cell type of the mouse airways, the Clara cell. Once these progressions of cancer in these models have been characterized, the role inflammation plays in the progression of cancer in these models will be determined. The analysis of these models includes state of the art imaging and DNA and proteomic analysis of the molecular changes during cancer progression.