Program Project in Models of Breast Cancer

乳腺癌模型项目

• 批准号: 7436667
• 负责人: LARRY NORTON
• 金额: $ 286.31万
• 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/7436667
• 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（由申请人提供）：该计划项目拨款申请提出了五个交互式实验室项目和两个核心项目，致力于通过研究小鼠模型在人类乳腺癌方面取得进展。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、发现和应用基因分型和表型分析的新方法以及使用 P01 开发的试剂在小鼠中执行治疗试验来实现协同作用和经济性。 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 重点研究与乳腺癌形成和进展有关的基因，应用基于禽类逆转录病毒载体的体内和体外基因递送至乳腺细胞。项目2描述了转移性乳腺癌细胞中TGF.的肿瘤抑制功能丧失的影响，并研究了介导小鼠和人类肺转移的肺转移基因表达特征，包括Id基因。项目3将使用Hsp90抑制剂以及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的联合调节，这已经取得了临床进展。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 将研究小鼠乳腺上皮细胞和癌症上皮细胞中条件性 Id 家族过度表达对肿瘤发生、进展和转移的影响，这些细胞源自几种明确的遗传背景。它将与其他项目合作，检查 Id1 变异模型的肿瘤起始和转移特性，并继续开发治疗药物。成像核心为这些项目提供先进的成像技术。拉里·诺顿和琼·马萨格担任项目总监和联合总监， 领导核心将提供分子阵列技术和生物统计学方面的专业知识。