RB ASSOCIATED PROTEIN 46 AND BREAST CANCER PROGRESSION

RB 相关蛋白 46 与乳腺癌进展

• 批准号: 6633588
• 负责人: ZHAO-YI WANG
• 金额: $ 19.24万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6633588
• 关键词: athymic mouse; brca gene; breast neoplasms; cell growth regulation; cell line; estradiol; estrogen inhibitor; gene induction /repression; guanine nucleotide binding protein; hormone regulation /control mechanism; immunocytochemistry; immunoprecipitation; neoplasm /cancer genetics; neoplastic process; polymerase chain reaction; retinoblastoma protein; tumor suppressor proteins

DESCRIPTION: (Adapted from the Investigator's Abstract): Based on their preliminary data that levels of RbAp46 expression decline during the progression of proliferative breast disease in the MCF10AT xenograft model and in malignant breast cancer cells, the investigators propose to: 1. Study the effects of constitutive expression on estrogen-stimulated progression using the MCF10AT xenograft model, and examine the levels of RbAp46 expression in human clinical samples using immunohistochemistry and/or RT-PCR. 2. Study the biological significance of the interaction between RbAp46 and the product of BRCA1 using in vivo and in vitro binding assays, as co-immunoprecipitation and GST capture assays, and RbAp46 and BRCA1 interaction and co-localization during the cell cycle and after exposure to DNA damage agents. 3. Study the molecular mechanisms by which RbAp46 inhibits cell growth and suppresses malignant transformation by examining the Ras pathway in MCF10At cells, and structure/ functional analyses to determine the domains of RbAp46 that are required for its growth inhibition and interaction with BRCA1.

描述：（根据调查员的摘要改编）：基于他们的 RBAP46表达水平下降的初步数据 MCF10AT异种移植模型中增殖性乳腺疾病的进展和 在恶性乳腺癌细胞中，研究人员建议：1。 本构表达对雌激素刺激的进展的影响 MCF10AT异种移植模型，并检查人类RBAP46的表达水平 使用免疫组织化学和/或RT-PCR的临床样品。 2 RBAP46与乘积之间相互作用的生物学意义 BRCA1使用体内和体外结合测定，作为共免疫沉淀和 GST捕获测定法，RBAP46和BRCA1相互作用和共定位 细胞周期和暴露于DNA损伤剂后。 3。研究分子 RBAP46抑制细胞生长并抑制恶性肿瘤的机制 通过检查MCF10AT细胞中的RAS途径以及结构/ 功能分析以确定RBAP46的域 它的生长抑制和与BRCA1的相互作用。