Focal Adhesion Kinase (FAK) in Human Neuroblastoma

人神经母细胞瘤中的粘着斑激酶 (FAK)

• 批准号: 8136297
• 负责人: Elizabeth A. Beierle
• 金额: $ 13.45万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8136297
• 关键词: Apoptosis; Attenuated; Basic Science; Binding Sites; Biological Assay; Biology; Cancer Center; Cell Death; Cell Line; Clinical; Clinical Trials; Data; Diagnostic Neoplasm Staging; Dominant-Negative Mutation; Electrophoretic Mobility Shift Assay; Extracellular Matrix; Florida; Focal Adhesion Kinase 1; Formalin; Funding; Goals; Growth; Histology; Human; Immunoblotting; Immunodeficient Mouse; Immunohistochemistry; In Vitro; Instruction; Intervention; Investigation; Knowledge; Laboratories; Lead; Luciferases; MYCN gene; Measures; Messenger RNA; Molecular Biology; Neoplasm Metastasis; Neural Crest; Neuroblastoma; Oncogenes; Operative Surgical Procedures; Paraffin Embedding; Pediatric Neoplasm; Preparation; Proteins; Regulation; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Scientist; Series; Signal Transduction; Signaling Molecule; Site; Site-Directed Mutagenesis; Small Interfering RNA; Specimen; Techniques; Testing; Tetracyclines; Time; Tissue Sample; Tissues; Training Programs; Transcriptional Regulation; Translating; Translations; Tumor stage; Universities; Xenograft Model; anticancer research; attenuation; career; cell motility; chromatin immunoprecipitation; clinically relevant; design; experience; expression vector; in vivo; in vivo Model; insight; killings; kinase inhibitor; mRNA Expression; mutant; neuroblastoma cell; novel; outcome forecast; overexpression; prognostic; programs; promoter; protein expression; skills; small molecule; transcription factor; treatment strategy; tumor; tumor growth; tumor progression; tumor xenograft; tumorigenesis

DESCRIPTION (provided by applicant): This proposed five year training program is designed to expand the applicant's knowledge in advanced molecular biology. The primary goals of the training program are to expand the applicant's ability in performing basic research into a hypothesis-driven, mechanistic understanding of tumorigenesis, and to provide her with the skills necessary to develop a productive, independently funded, laboratory. To accomplish these goals, a rigorous training program has been proposed, including didactic instruction in advanced molecular biology, fundamental instruction in the conduct of clinical investigation, and a research experience focusing on advanced laboratory techniques. The training program has been thoughtfully constructed to help the applicant achieve her long term career goal of the investigation of novel treatment strategies for neuroblastoma. The research program incorporates several unique aspects available at the University of Florida, namely the University of Florida Shands Cancer Center with expertise of a number of scientists in the field of cancer research, and the Department of Surgery Cancer Research Laboratory with its pioneering discoveries in the biology of focal adhesion kinase (FAK). The proposed research focuses on the expression and function of FAK in neuroblastoma, a childhood tumor with a dismal prognosis. This proposal builds upon preliminary data demonstrating a correlation between FAK expression and MYCN oncogene amplification, and the effects of attenuation of FAK upon cellular survival. We hypothesize that FAK is overexpressed in neuroblastomas with MYCN amplification and that MYCN is involved in the transcriptional regulation of FAK. We will study FAK expression in human neuroblastoma tissue samples and cell lines, measure the effects of FAK upon cellular attachment, proliferation, motility, and survival, and determine the effects of FAK inhibition upon tumor growth and survival in an in vivo model of neuroblastoma. Better insight into the relationship between FAK and MYCN offers the potential for translating this knowledge into clinically relevant therapies for this devastating childhood tumor.

描述（由申请人提供）：拟议的五年培训计划旨在扩大申请人在高级分子生物学方面的知识。培训计划的主要目标是将申请人进行基础研究的能力扩大到对肿瘤发生的假设驱动的机械理解，并为她提供开发富有成效的，独立资助的实验室所需的技能。为了实现这些目标，已经提出了一项严格的培训计划，包括高级分子生物学的教学教学，进行临床研究的基本指导以及针对高级实验室技术的研究经验。该培训计划经过深思熟虑的构建，以帮助申请人实现她对神经母细胞瘤新型治疗策略进行调查的长期职业目标。该研究计划结合了佛罗里达大学（University of Florida）的几个独特方面，即佛罗里达大学Shands癌症中心，具有癌症研究领域的许多科学家的专业知识，以及外科癌症研究部实验室的研究，并在焦点粘附激酶生物学生物学（FAK）中发现了开拓性的发现。拟议的研究重点是FAK在神经母细胞瘤中的表达和功能，神经母细胞瘤是一种较沮丧的预后。该建议基于初步数据，表明FAK表达与霉菌癌基因扩增之间存在相关性，以及FAK衰减对细胞存活的影响。我们假设FAK在神经母细胞瘤中过表达，并具有MYCN扩增，并且MYCN参与了FAK的转录调控。我们将研究人类神经母细胞瘤组织样品和细胞系中的FAK表达，测量FAK对细胞附着，增殖，运动和存活的影响，并确定FAK抑制对肿瘤生长的影响和在神经母细胞瘤的体内模型中的影响。更好地洞悉FAK和MYCN之间的关系，可以将这些知识转化为这种毁灭性儿童肿瘤的临床相关疗法。

项目成果

MYCN, neuroblastoma and focal adhesion kinase (FAK).

• DOI: 10.2741/e257
• 发表时间: 2011-01-01
• 期刊: Frontiers in bioscience (Elite edition)
• 作者: Beierle EA