MAMMAGLOBIN AND ITS ROLE IN HUMAN BREAST CANCER

乳房珠蛋白及其在人类乳腺癌中的作用

• 批准号: 2856479
• 负责人: TIMOTHY Peter FLEMING
• 金额: $ 13.41万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2856479
• 关键词: biomarker; breast neoplasms; cell proliferation; corticosteroid binding protein; disease /disorder etiology; gene expression; gene targeting; genetic promoter element; genetic regulation; genetically modified animals; laboratory mouse; mammalian embryology; phenotype; protein biosynthesis; protein metabolism; proteins; serology /serodiagnosis

DESCRIPTION (Adapted from the applicant's abstract): The goal of this proposal is to understand the biological role of mammaglobin in breast cell biology. This breast cancer gene is expressed exclusively in the mammary gland and overexpression is observed in 25% of all primary breast cancers examined to date. It has been demonstrated that mammaglobin is a secreted protein and that mammaglobin synthesis correlates with proliferating breast tissue. Work is in progress using mammaglobin as a relevant serum marker for the detection of breast cancer; the detection of contaminating breast tumor cells in peripheral stem cell products; and as an antigen for a breast tumor vaccine. Mammaglobin is a member of the uteroglobin gene family which includes uteroglobin, Clara Cell 10 kD protein, mouse androgen binding protein, and prostatein. These protein products have been shown to be regulated by steroids, secreted from epithelial cells, act as regulators of inflammatory responses, or bind steroid ligands. The hypothesis to be tested is that mammaglobin is essential to mammary gland biology and that the dysregulation of mammaglobin has a role in the etiology of some breast cancers. To address these goals, Dr. Fleming proposes the following specific aims: 1. Using epitope-taged mammaglobin, identify the mammaglobin protein complex and determine if mammaglobin is a steroid binding protein. 2. Test the hypothesis that mammaglobin expression contributes to the tumor phenotype. 3. Identify the cis-acting elements of the promoter that confers mammary-specific expression. 4. Identify the murine homolog to mammaglobin; examine its pattern of expression in the developing embryo, and initiate studies to examine phenotypic alterations in a murine knockout model for the mammaglobin gene.

描述（改编自申请人的摘要）：本项目的目标 提议是了解乳腺细胞中乳腺珠蛋白的生物学作用 生物学。 这种乳腺癌基因仅在乳腺中表达 25% 的原发性乳腺癌中观察到腺体和过度表达 迄今为止已检查过。 研究表明，乳腺珠蛋白是一种分泌型 蛋白质以及乳房珠蛋白合成与乳房增殖相关 组织。 使用乳房珠蛋白作为相关血清标记物的工作正在进行中 用于检测乳腺癌；检测污染性乳房 外周干细胞产品中的肿瘤细胞；并作为乳房的抗原 肿瘤疫苗。 乳房珠蛋白是子宫珠蛋白基因家族的成员， 包括子宫珠蛋白、Clara Cell 10 kD 蛋白、小鼠雄激素结合 蛋白质和前列腺素。 这些蛋白质产品已被证明 受上皮细胞分泌的类固醇调节，充当调节剂 炎症反应，或结合类固醇配体。 假设为 经测试，乳腺珠蛋白对于乳腺生物学至关重要，并且 乳房珠蛋白的失调在某些乳房的病因学中起作用 癌症。 为了实现这些目标，弗莱明博士提出以下建议 具体目标： 1. 使用表位标记的乳房珠蛋白，鉴定 乳房珠蛋白复合物并确定乳房珠蛋白是否是类固醇 结合蛋白。 2. 检验乳房珠蛋白表达的假设 有助于肿瘤表型。 3. 确定顺式作用元件 赋予乳腺特异性表达的启动子。 4. 识别 小鼠乳腺珠蛋白同源物；检查其表达模式 发育中的胚胎，并启动研究以检查表型变化 乳腺珠蛋白基因的小鼠敲除模型。