Transcriptional regulation of NC precursor formation

NC 前体形成的转录调控

• 批准号: 7126775
• 负责人: Carole LaBonne
• 金额: $ 20.49万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-26 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126775
• 关键词: Xenopus oocyte; acyltransferase; cell growth regulation; cell line; cell migration; developmental genetics; developmental neurobiology; genetic transcription; microarray technology; neoplasm /cancer invasiveness; neoplastic growth; neural crest; nonmammalian vertebrate embryology; protooncogene; transcription factor

DESCRIPTION (provided by applicant): Neural crest cells are multi-potent, migratory, tissue-invasive cells that originate in the ectoderm of vertebrate embryos and play a central role in the development of the vertebrate body plan. A number of devastating cancers, including melanoma and neuroblastoma, are cancers of the neural crest. Moreover, neural crest cells share a number of general characteristics with metastatic tumor cells, and these two cell types have key molecular mediators in common, including Snail-family repressors and c-myc. This proposal seeks to exploit the considerable advantages of the Xenopus system in order to better understand the roles played by Snail-related factors and c-myc during normal neural crest development and in tumorigenesis, including the acquisition of invasiveness. The aims of the grant include: 1) determining the molecular mechanisms that underlie the distinct activities of Snail-family proteins during neural crest precursor formation, neural crest emigration, and during epithelial-to-mesenchymal transitions (EMTs) in tumor cells; 2) determining if c-myc regulates the expression of neural crest target genes by recruiting HAT activity to target promoters, and determining if Id3 functions as a Myc-effector during neural crest formation; 3) using cDNA macroarray-based gene discovery methods to identify the key transcriptional targets of c-myc and Snail-family repressors during neural crest precursor cell formation, and during the onset of neural crest migration and 4) testing the hypothesis that such targets will also play roles in tumor progression by examining the expression of these factors, and the effects of over-expressing these factors, in a panel of epithelial tumor cell lines

描述（由申请人提供）：神经嵴细胞是多能、迁移、组织侵袭性细胞，起源于脊椎动物胚胎的外胚层，在脊椎动物身体计划的发育中发挥核心作用。许多毁灭性的癌症，包括黑色素瘤和神经母细胞瘤，都是神经嵴癌症。此外，神经嵴细胞与转移性肿瘤细胞具有许多共同特征，并且这两种细胞类型具有共同的关键分子介质，包括 Snail 家族阻遏物和 c-myc。 该提案旨在利用非洲爪蟾系统的显着优势，以便更好地了解 Snail 相关因子和 c-myc 在正常神经嵴发育和肿瘤发生（包括获得侵袭性）中所发挥的作用。该资助的目的包括：1) 确定 Snail 家族蛋白在神经嵴前体形成、神经嵴迁移和肿瘤细胞上皮间质转化 (EMT) 过程中独特活性的分子机制； 2)确定c-myc是否通过向靶启动子募集HAT活性来调节神经嵴靶基因的表达，并确定Id3在神经嵴形成过程中是否充当Myc效应子； 3) 使用基于 cDNA 宏阵列的基因发现方法来识别 c-myc 和 Snail 家族阻遏物在神经嵴前体细胞形成过程中以及神经嵴迁移开始过程中的关键转录靶标，以及 4) 通过检查这些因子的表达以及在一组上皮肿瘤中过度表达这些因子的影响，测试这些靶标也在肿瘤进展中发挥作用的假设 细胞系