Molecular basis of E-cadherin transcriptional regulation

E-钙粘蛋白转录调控的分子基础

• 批准号: 6791596
• 负责人: ROBERT J SIMS
• 金额: $ 4.73万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6791596
• 关键词: DNA binding protein; SDS polyacrylamide gel electrophoresis; cadherins; cell adhesion molecules; chromatin immunoprecipitation; gene expression; gene induction /repression; genetic regulation; genetic transcription; laboratory rabbit; mass spectrometry; neoplasm /cancer invasiveness; neoplastic process; postdoctoral investigator; recombinant proteins; western blottings

DESCRIPTION (provided by applicant): Our understanding of cancer initiation far exceeds our knowledge of tumor progression. The cell adhesion molecule E-cadherin contributes to aspects of tumor formation and invasion. The DNA-binding proteins Snail and Slug mediate E-cadherin transcriptional repression, and regulate aspects of carcinogenesis and cell survivability. While much has been learned regarding Snail and Slug biological function, the molecular mechanisms of Snail and Slug mediated transcriptional repression are not well understood. The studies in this proposal aim to determine the molecular mechanisms of Snail and Slug repression in the context of the E-cadherin promoter. First, specific activation of the E-cadherin promoter will be reconstituted in vitro, followed by biochemical studies to elucidate the mechanisms of Snail and Slug repression of E-cadherin. Finally, studies in vivo will be performed to complement the biochemical approaches, and examine E-cadherin transcriptional regulation in living cells. These studies will provide insight into the basis of Snail and Slug repression and E-cadherin silencing, and may potentially identify key components of tumor establishment and invasion.

描述（由申请人提供）： 我们对癌症发生的了解远远超过了对肿瘤进展的了解。细胞粘附分子 E-钙粘蛋白有助于肿瘤形成和侵袭。 DNA 结合蛋白 Snail 和 Slug 介导 E-钙粘蛋白转录抑制，并调节癌发生和细胞存活率。虽然人们对 Snail 和 Slug 的生物学功能了解很多，但 Snail 和 Slug 介导的转录抑制的分子机制尚不清楚。本提案中的研究旨在确定 E-钙粘蛋白启动子背景下 Snail 和 Slug 抑制的分子机制。首先，将在体外重建E-钙粘蛋白启动子的特异性激活，随后进行生化研究以阐明Snail和Slug抑制E-钙粘蛋白的机制。 最后，将进行体内研究以补充生化方法，并检查活细胞中的 E-钙粘蛋白转录调控。这些研究将深入了解 Snail 和 Slug 抑制以及 E-钙粘蛋白沉默的基础，并可能确定肿瘤形成和侵袭的关键组成部分。