Program Project in Models of Breast Cancer

乳腺癌模型项目

• 批准号: 8063126
• 负责人: LARRY NORTON
• 金额: $ 291.47万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063126
• 关键词: Program; Project; Models; Breast; Cancer

DESCRIPTION (provided by applicant): This Program Project Grant application presents five interactive laboratory projects and two cores dedicated to making progress against human breast cancer by studying mouse models. It achieves synergy and an economy of effort by sharing existing strains, collaboratively developing new strains, designing and using an Imaging Core, discovering and applying new methods for genotyping and phenotyping, and the execution of therapeutic trials in mice using P01-developed reagents. Active cancer clinicians in the P01 are committed to assuring a meaningful impact on clinical thinking, education, and research. Project 1 focuses on the genes implicated in mammary cancer formation and progression, applying avian retroviral vector-based delivery of genes to mammary cells in vivo and iin vitro. Project 2 delineates the effects of the loss of TGF.'s tumor-suppressive function in metastatic breast cancer cells and studies a lung metastasis gene expression signature, including Id genes, that mediates pulmonary metastasis in mouse and human. Project 3 will use Hsp90 inhibitors and selective inhibitors of PI3K and AKt to determine the role of PI3K/AKt signaling in cancer, and continue to explore joint Hsp90 and HER2 modulation, which has already led to a clinical advance. Project 4 will characterize mammary tumors and their lung metastases occurring in HDR-deficient mammary epithelium. It will evaluate genetic instability in diverse mouse models to define the DNA damage response in normal, repair-deficient and oncogene-induced mammary epithelium. Project 5 will examine the effects on tumor initiation, progression, and metastasis of conditional Id-family over-expression in murine mammary epithelial cells and cancer epithelial cells arising from several well-defined genetic backgrounds. In collaboration with other projects it will examine the tumor-initiating and metastatic properties of Id1-variant models, and continue to develop therapeutic agents. The Imaging Core supplies advanced imaging technology to these projects. Larry Norton and Joan Massague serve as Program Director and Co-Director, and a Leadership Core will offer expertise in molecular array technology and biostatistics.

描述(由申请者提供)：该计划项目资助申请提供了五个互动实验室项目和两个核心项目，致力于通过研究老鼠模型来对抗人类乳腺癌。它通过共享现有菌株、合作开发新菌株、设计和使用成像核心、发现和应用新的基因分型和表型方法，以及使用P01开发的试剂在小鼠身上执行治疗试验，实现了协同效应和工作成本。P01中活跃的癌症临床医生致力于确保对临床思维、教育和研究产生有意义的影响。项目1主要研究与乳腺癌形成和发展有关的基因，将基于禽类逆转录病毒载体的基因导入体内和体外的乳腺细胞。项目2描述了失去转化生长因子的影响。S在转移性乳腺癌细胞中的肿瘤抑制功能，并研究了肺转移基因的表达特征，包括ID基因，它介导了小鼠和人的肺转移。项目3将使用Hsp90抑制剂和PI3K和AKT的选择性抑制剂来确定PI3K/AKT信号在癌症中的作用，并继续探索Hsp90和HER2的联合调控，这已经导致了临床的进展。项目4将描述发生在HDR缺陷的乳腺上皮中的乳腺肿瘤及其肺转移。它将评估不同小鼠模型中的遗传不稳定性，以确定正常、修复缺陷和癌基因诱导的乳腺上皮中的DNA损伤反应。项目5将研究条件性ID家族在小鼠乳腺上皮细胞和来自几个明确遗传背景的癌细胞中过度表达对肿瘤起始、进展和转移的影响。它将与其他项目合作，检查Id1变异模型的肿瘤启动和转移特性，并继续开发治疗剂。成像核心为这些项目提供先进的成像技术。拉里·诺顿和琼·马萨格担任项目主任和联席主任， 领导核心公司将提供分子阵列技术和生物统计学方面的专业知识。