Program Project in Models of Breast Cancer

描述（由申请人提供）： 该计划项目资助申请提出了一个协调的，互动的实验室项目组和核心资源，通过关注乳腺癌和使用人类疾病的小鼠模型来团结起来。 它通过共享现有菌株、合作开发新菌株（例如，双转基因小鼠），配置和使用一个新的核心设施的小鼠肿瘤成像，合作发现和选择性使用新的方法来表征基因型和表型，以及设计，进行和分析的治疗试验，在实验室动物使用药物和其他试剂内开发的P01。 由于积极的癌症临床医生本质上参与了这些努力，在我们的实验室获得的知识将对临床思维，教育和研究产生直接和实质性的影响。 Harold Varmus博士领导的项目1研究了人类乳腺癌小鼠模型以及卵巢和胰岛细胞瘤形成相关模型中肿瘤进展的决定因素。 Joan Massague博士领导的项目2涉及TGF-β信号通路。 项目3由Neal罗森博士领导，开发安莎霉素抗生素作为癌症生物学研究的治疗剂和试剂。 项目4由Maria Jasin和玛丽Ellen Moynahan博士领导，探讨了BRCA 1和BRCA 2突变引起的同源修复缺陷的后果。 项目5，根据Dr. Robert Benezra关注Id基因及其与新生血管形成的关系。 一个成像核心，在博士史蒂芬拉森和尤里Tjuvajev，提供先进的成像技术的项目。 Larry Norton博士担任首席研究员，Joan Massague博士担任共同首席研究员，Agnes Viale博士担任分子阵列技术协调员。

DESCRIPTION (provided by applicant): This Program Project Grant application presents a coordinated, interactive group of laboratory projects and a core resource, united by a concern with breast cancer and by the use of mouse models of the human disease. It achieves scientific synergy and an economy of effort by the sharing of existing strains, the collaborative development of new strains (e.g., bi-transgenic mice), the configuration and use of a new core facility for the imaging of mouse tumors, the cooperative discovery and selective use of new methods for the characterization of genotypes and phenotypes, and the design, conduct, and analysis of therapeutic trials in laboratory animals using drugs and other reagents developed within the P01. Because active cancer clinicians are intrinsically involved in these efforts, the knowledge gained In our laboratories will have a direct and substantial impact on clinical thinking, education, and research. Project 1, under Dr. Harold Varmus, examines the determinants of tumor progression in mouse models of human breast cancer and related models of ovarian and islet cell neoplasia. Project 2, under Dr. Joan Massague, concerns the TGF-beta eta signaling pathway. Project 3, under Dr. Neal Rosen, develops the ansamycin antibiotics as therapeutic agents and reagents for the study of cancer biology. Project 4, under Drs. Maria Jasin and Mary Ellen Moynahan, explores the consequences of defective homologous repair incurred through BRCA1 and BRCA2 mutations. Project 5, underDr. Robert Benezra, concerns the Id genes and their relation to neoangiogenesis. An Imaging Core, under Drs. Steven Larson and Juri Tjuvajev, supplies advanced imaging technology to the Projects. Dr. Larry Norton serves as Principal Investigator, Dr. Joan Massague as Co-Principal Investigator, and Dr. Agnes Viale as Coordinator of Molecular Array Technologies.