RB ASSOCIATED PROTEIN 46 AND BREAST CANCER PROGRESSION

RB 相关蛋白 46 与乳腺癌进展

• 批准号: 6377691
• 负责人: ZHAO-YI WANG
• 金额: $ 23.49万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 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/6377691
• 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：（改编自研究者摘要）：基于他们的 初步数据表明，RbAp 46的表达水平下降， MCF 10AT异种移植模型中增殖性乳腺疾病的进展， 在恶性乳腺癌细胞中，研究人员建议：1.研究 组成型表达对雌激素刺激进展的影响 MCF 10AT异种移植物模型，并检查人MCF 10AT中RbAp 46表达水平。 使用免疫组织化学和/或RT-PCR检测临床样品。2.研究 RbAp 46与蛋白产物相互作用的生物学意义 使用体内和体外结合试验，作为免疫共沉淀和 GST捕获测定，以及RbAp 46和BRCA 1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 RbAp 46抑制细胞生长和抑制恶性肿瘤的机制 通过检查MCF 10At细胞中的Ras途径，以及结构/ 功能分析，以确定RbAp 46的结构域， 其生长抑制和与BRCA 1的相互作用。