Mouse Models for Tumor Progression and Maintenance

用于肿瘤进展和维持的小鼠模型

• 批准号: 7438484
• 负责人: HAROLD E. VARMUS
• 金额: $ 40.79万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7438484
• 关键词: Affect; Animal Model; Animals; Behavior; Biochemical Genetics; Biological Assay; Birds; Breast; Breast Cancer Model; Breast Carcinoma; Candidate Disease Gene; Cell Shape; Cells; Dependence; Development; Dominant-Negative Mutation; E-Cadherin Staining Method; Elements; Event; Family; Fibroblast Growth Factor; Funding; Gene Combinations; Gene Delivery; Genes; Genetic; Genotype; Genus Alpharetrovirus; Human; Hyperplasia; Intestines; Invasive; Islet Cell; Islet Cell Tumor; Islets of Langerhans; Learning; Lesion; Maintenance; Malignant Neoplasms; Mammary Neoplasms; Mammary Tumorigenesis; Mammary gland; Mediating; Mediator of activation protein; Medullary carcinoma; Methods; MicroRNAs; Modeling; Molecular; Movement; Mus; Mutation; Neoplasm Metastasis; Neoplasms; Oncogenes; Oncogenic; Organ; Ovarian; Pancreas; Pathway interactions; Pharmaceutical Preparations; Phenotype; Pongidae; Protein Kinase C; Protein Kinase C Inhibitor; Proto-Oncogenes; Retroviral Vector; Role; Sampling; Series; Signal Pathway; Signal Transduction; Simulate; System; Testing; Tetracycline; Tetracyclines; Transgenes; Viral Vector; Virus; Work; base; carcinogenesis; cell transformation; in vitro Assay; in vivo; lymph nodes; malignant breast neoplasm; mammary epithelium; member; mouse model; mutant; neoplastic cell; novel; programs; tissue culture; tool; tumor; tumor progression; tumorigenesis; vector

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.

癌症是由一系列有待充分描述的遗传和生化事件引起和发展的。 在支持该项目的初期，我们对几种小鼠乳腺模型进行了表征 通过检查形态特征、淋巴结依赖性、基因型和表达来诊断癌症 Wnt 信号元件的表型和肿瘤发生机制。我们也学会了交付 病毒载体转移至乳腺和胰岛细胞，并已证实两个候选基因能够 促进胰岛细胞肿瘤进展。在新的提案中，我们继续使用多种鼠标模型 乳腺癌和胰岛细胞癌变模型，以及三维组织培养方法和 来自储存的人类肿瘤样本的材料，探索与分子基础相关的几个问题 瘤形成。病毒载体将用于评估许多基因和 micro-RNA 作为肿瘤的贡献者 胰腺癌和乳腺癌模型的进展。我们将努力理解这一现象 通过使用条件致癌转基因和病毒载体来识别致癌基因依赖性的因素 保护肿瘤免受癌基因依赖性。我们将探索肿瘤发生的初步证据 Wnt 信号通路的成分由成纤维细胞生长因子或蛋白质成员介导 激酶 C (PKC) 家族。