FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS

NF2基因突变的功能分析

• 批准号: 6193800
• 负责人: David H Gutmann
• 金额: $ 33.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-28 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6193800
• 关键词: RNA splicing; Schwann cells; athymic mouse; biological signal transduction; cell growth regulation; cell line; cell motility; confocal scanning microscopy; flow cytometry; gene expression; gene mutation; intermolecular interaction; neoplastic process; neoplastic transformation; neurofibromatosis; neurogenetics; polymerase chain reaction; protein isoforms; protein structure function; transfection; tumor suppressor proteins; western blottings

DESCRIPTION (From the applicant's abstract): Little is known about the molecular pathogenesis of nervous system tumors such as meningiomas and schwannomas. Individuals affected with neurofibromatosis 2 (NF2) develop these tumors at increased frequency. In addition, mutations and loss of NF2 gene expression are associated with the development of sporadic schwannomas and meningiomas, suggesting that the NF2 gene product, merlin is a critical growth regulator for Schwann cells and meningeal cells. The NF2 tumor suppressor gene bears sequence similarity to Protein4.1 proteins that link the actin cytoskeleton to cell surface glycoproteins. Previous work from out laboratory has demonstrated that merlin regulates cell motility and proliferation as well as cell spreading. In this application we propose to test the hypothesis that merlin integrates several different several cellular processes important for tumor formation and progression reflected by its ability to regulate cell spreading (tumor initiation), cell proliferation (tumor growth) and cell motility (tumor spread). The experiments proposed in this application are aimed at determining how the merlin tumor suppressor functions as a negative growth regulator by defining merlin functional domains, critical merlin protein interactions and relevant intracellular signaling pathways. Our ability to design rational therapies for schwannomas and meningiomas is dependent on an improved understanding of the mechanisms by which loss of merlin expression and function promotes tumor formation.

描述（摘自申请人摘要）：我们对……知之甚少