Signaling and Progression in Prostate Cancer

前列腺癌的信号传导和进展

• 批准号: 8338790
• 负责人: Bryce Paschal
• 金额: $ 174.13万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-23 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8338790
• 关键词: 1-Phosphatidylinositol 3-Kinase; Address; Adrenal Glands; American; Androgen Receptor; Androgens; Biochemical; Biological Markers; Cancer Biology; Castration; Cause of Death; Cell Proliferation; Cell physiology; Cells; Charcoal; Clinical; Collaborations; Colorado; Communication; Development; Disease; Drug Delivery Systems; Emerging Technologies; Engineering; Figs - dietary; Funding; Gene Expression; Genes; Genetic; Goals; Gray unit of radiation dose; Growth; Guanosine Triphosphate Phosphohydrolases; Hormones; Human; Hypoxia; Image; Instruction; Intervention; Investigation; Link; Malignant Neoplasms; Malignant neoplasm of prostate; MicroRNAs; Modeling; Molecular; Mus; Neoplasm Metastasis; Outcome; Output; Oxygen; Pathway interactions; Phosphotransferases; Pre-Clinical Model; Production; Productivity; Prostate; Prostatic Neoplasms; Proteins; Proto-Oncogene Proteins c-akt; Refractory; Regulation; Research; Research Personnel; Resistance; Scientist; Serum; Signal Transduction; Signal Transduction Pathway; Site; Staging; Time; Tissues; Transgenic Animals; Transgenic Model; Translating; Universities; Virginia; Vision; Xenograft procedure; bone; cancer cell; design; experience; human disease; knowledge base; member; men; mouse model; neoplastic cell; novel; novel therapeutics; prognostic; programs; sensor; tumor growth; tumor progression; tumorigenesis

DESCRIPTION (provided by applicant): The median survival time of men with prostate cancer that progresses to androgen independence is approximately two years. The goal of our Program is to elucidate the alterations in signal transduction and associated changes in gene expression that underlie prostate progression to the androgen independent state. Our Program brings together productive and experienced investigators at the University of Virginia and the University of Colorado with the complementary expertise needed to fulfill the stated goals. Our team includes experts in basic and clinical aspects of human prostate cancer biology (D. Theodorescu; Colorado), signal transduction and the androgen receptor (B. Paschal; Virginia), and microRNA regulation (A. Dutta; Virginia). Project 1 will determine how hypoxic signals are sensed by post-translational mechanisms and transduced into changes in gene expression that promote prostate cancer progression, including metastasis. Project 2 will use new mouse models to determine how kinases downstream of PI-3 kinase cooperate to drive prostate tumorigenesis. Project 3 will determine how changes in microRNA profiles regulate cell proliferation and prostate cancer progression to androgen independence. The three Projects are supported by three Cores that have a strong track record of providing support for Program members. Core A (Administration; Director, B. Paschal) will enhance productivity by facilitating communication between the Virginia and Colorado sites, and by fulfilling biostatistical needs (Biostatistician, M. Conaway) of the Program. Core B (Transgenic Models and Animal Imaging; Director, David Wotton) is directed by a mouse genetics expert who will develop genetically engineered murine models for prostate tumorigenesis, and assist with xenograft production. Core C (Tissue Analysis; Director, H. Frierson) will perform histological and immunohistochemical analysis of mouse and human prostate. Our team of basic and clinician scientists has a track record of collaboration and a shared vision of defining prostate cancer progression mechanisms. The long-term objective is to translate our understanding of prostate cancer progression mechanisms into the identification of new drug targets and pre-clinical models that recapitulate key aspects of the human disease.

描述（由申请人提供）：前列腺癌男性的中位生存时间大约为两年。我们程序的目的是阐明信号转导的变化以及基因表达的相关变化，这些变化是前列腺发展为雄激素独立状态的基础。我们的计划汇集了弗吉尼亚大学和科罗拉多大学的富有成效和经验丰富的研究人员，并汇集了实现既定目标所需的补充专业知识。我们的团队包括人类前列腺癌生物学基本和临床方面的专家（D. theodorescu; Colorado），信号转导和雄激素受体（B. paschal; Virginia）和MicroRNA调节（A. Dutta; Dutta; Virginia）。项目1将通过翻译后机制来确定如何感测低氧信号，并转化为基因表达的变化，这些变化促进了包括转移在内的前列腺癌进展。项目2将使用新的小鼠模型来确定PI-3激酶下游的激酶如何配合以驱动前列腺肿瘤发生。项目3将确定microRNA谱的变化如何调节细胞增殖和前列腺癌的进展到雄激素独立性。这三个项目得到了三个核心的支持，这些核心在为计划成员提供支持方面有很强的记录。核心A（管理； B. Paschal主任）将通过促进弗吉尼亚州和科罗拉多州站点之间的沟通，以及满足该计划的生物统计需求（Biostatisticians，M。Conaway）来提高生产率。 Core B（转基因模型和动物成像；导演David Wotton）由小鼠遗传学专家指导，该专家将开发用于前列腺肿瘤发生的基因工程鼠模型，并有助于产生异种移植。 Core C（组织分析；H。Frierson主任）将对小鼠和人类前列腺进行组织学和免疫组织化学分析。我们的基础和临床医生团队具有协作的记录以及定义前列腺癌进度机制的共同愿景。长期目标是将我们对前列腺癌进度机制的理解转化为新药靶标和临床前模型的识别，这些模型概括了人类疾病的关键方面。