Bin1 in E2F1-Mediated Tumor Growth Suppression

E2F1 介导的肿瘤生长抑制中的 Bin1

• 批准号: 6828673
• 负责人: Erica K Cassimere
• 金额: $ 3.58万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6828673
• 关键词: MCF7 cell; apoptosis; cell line; cell morphology; cell senescence; cellular oncology; flow cytometry; molecular oncology; neoplasm /cancer genetics; neoplastic cell; neoplastic growth; nuclear proteins; p53 gene /protein; predoctoral investigator; prostate neoplasms; protein protein interaction; protein structure function; small interfering RNA; transcription factor; tumor suppressor proteins

DESCRIPTION (provided by applicant): The long-term objectives of my Ph.D. thesis project is to define the pathophysiological mechanisms underlying tumor suppression mediated by Bin1 and the E2F1 transcription factor at the molecular and cellular levels. My preliminary results strongly suggest that Bin1 functionally interacts with E2F1 in LNCaP (where p53 is intact) and DU145 (where p53 is mutated) prostate cancer cell lines to reduce cell growth rate. I hypothesize that Bin1 plays a role in the E2Fl-dependent growth suppression independently of p53. The specific aims of this proposed study are to determine whether Bin1 is necessary for E2Fl-dependent growth suppression and vice versa, and to define the role of Bin1 in apoptosis or senescence induced by E2F1. I also aim to assess whether p73, a p53 gene homologue and a direct transcriptional target of E2F1, is required for the growth suppression by Bin1. I wilt use colony formation assay, small-interfering RNA, and biochemical and molecular cell biological techniques using human cancer cell lines. Because neither apoptosis nor senescence mediated by E2F1 occurs naturally in cancer cells, the exact mechanism through which Bin1 and E2F1 act in cancer cells has emerged as a major question in cancer biology.

描述（由申请人提供）：我的博士学位的长期目标。论文项目是为了定义由BIN1介导的肿瘤抑制和E2F1转录因子在分子和细胞水平上介导的病理生理机制。我的初步结果强烈表明BIN1在LNCAP中与E2F1（其中p53完整）和DU145（其中p53被突变）前列腺癌细胞系与E2F1相互作用，以降低细胞的生长速率。我假设BIN1在p53独立于E2FL依赖性生长抑制中起作用。这项拟议的研究的具体目的是确定BIN1对于E2FL依赖性生长抑制是必需的，反之亦然，并确定BIN1在E2F1引起的凋亡或衰老中的作用。我还旨在评估p73，p53基因同源物和e2f1的直接转录靶标是否是BIN1抑制生长所必需的。我使用菌落形成测定法，小裂化RNA以及使用人类癌细胞系的生化和分子细胞生物学技术。由于E2F1介导的凋亡和衰老都不发生在癌细胞中，因此BIN1和E2F1在癌细胞中起作用的确切机制已成为癌症生物学的主要问题。