Mouse Models for Tumor Progression and Maintenance

癌症的发生和发展是由一系列遗传和生物化学事件引起的，这些事件仍有待充分描述。 在支持该项目的最初阶段，我们对几种小鼠乳腺模型进行了表征， 通过检查癌的形态学特征、淋巴结依赖性、其基因型和表达 表型和通过Wnt信号传导元件的肿瘤发生机制。我们也学会了如何 已经证实了两个候选基因的能力， 促进胰岛细胞中的肿瘤进展。在新的提案中，我们继续使用各种鼠标模型 乳腺癌和胰岛细胞癌变模型，加上三维组织培养方法， 材料从储存的人类肿瘤样本，探讨有关的分子基础的几个问题， 肿瘤形成病毒载体将用于评估许多基因和微RNA作为肿瘤的贡献者 胰腺癌和乳腺癌模型的进展。我们将试图理解这一现象 通过使用条件致癌转基因和病毒载体来鉴定致癌基因依赖性的因素， 保护肿瘤免于癌基因依赖。我们将探索我们的初步证据， Wnt信号通路的组成部分是由成纤维细胞生长因子或蛋白质的成员介导的 激酶C（PKC）家族。

Cancers arise and progress by a series of genetic and biochemical events that remain to be fully described. During the initial period of support for this project, we have characterized several mouse models of breast carcinoma by examining morphological features, lymph node dependence, their genotypes and expression phenotypes, and mechanisms of oncogenesis by Wnt signaling elements. We have also learned to deliver viral vectors to mammary and pancreatic islet cells and have confirmed the ability of two candidate genes to promote tumor progression in islet cells. In the new proposal, we continue to use a variety of mouse models of breast cancer and a model of islet cell carcinogenesis, plus three dimensional tissue culture methods and materials from stored human tumor samples, to explore several issues related to the molecular basis of neoplasia. Virus vectors will be used to assess many genes and micro-RNAs as contributors to tumor progression in the pancreatic and mammary cancer models. We will seek to understand the phenomenon of oncogene dependence by using conditional oncogenic transgenes and viral vectors to identify factors that protect tumors from oncogene-dependence. And we will explore our preliminary evidence that oncogenesis by components of Wnt signaling pathways is mediated by fibroblast growth factors or members of the protein kinase C (PKC) family.