MAMMAGLOBIN AND ITS ROLE IN HUMAN BREAST CANCER

描述（改编自申请人的摘要）：本研究的目标 这项提案旨在了解乳腺珠蛋白在乳腺细胞中的生物学作用， 生物学 这种乳腺癌基因只在乳腺癌细胞中表达。 在所有原发性乳腺癌的25%中观察到腺体和过度表达 检查到目前为止。 已经证明，乳房珠蛋白是一种分泌的 乳腺珠蛋白的合成与乳腺增生有关 组织. 使用乳房珠蛋白作为相关血清标志物的工作正在进行中 用于检测乳腺癌;检测污染的乳房 外周干细胞产物中的肿瘤细胞;以及作为乳腺癌的抗原 肿瘤疫苗 乳腺珠蛋白是子宫珠蛋白基因家族的成员， 包括子宫珠蛋白、Clara细胞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是 由上皮细胞分泌的类固醇调节，作为 炎症反应或结合类固醇配体。 假设是 乳房珠蛋白对乳腺生物学是必需的， 乳房珠蛋白调节异常在某些乳房的病因中发挥作用 癌的 为了实现这些目标，弗莱明博士提出了以下建议 具体目标：1. 使用表位标记的乳房珠蛋白， 乳房珠蛋白蛋白复合物，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 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 与乳腺珠蛋白同源的鼠类;检查其在乳腺癌中的表达模式。 发展胚胎，并启动研究，以检查表型改变， 一种乳腺珠蛋白基因的小鼠敲除模型。

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.