MAMMAGLOBIN AND ITS ROLE IN HUMAN BREAST CANCER

描述(改编自申请人的摘要)：本报告的目标 建议了解乳房巨球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中表达。 在所有的原发乳腺癌中，有25%的乳腺癌有腺体和过表达。 到目前为止已经检查过了。已有研究表明，巨噬细胞球蛋白是一种分泌的 蛋白质和乳房巨球蛋白的合成与乳腺增生症相关 组织。将乳头球蛋白用作相关血清标记物的研究正在进行中 用于检测乳腺癌；检测污染的乳房 外周干细胞产品中的肿瘤细胞；以及作为乳房的抗原 肿瘤疫苗。乳大球蛋白是子宫红蛋白基因家族的一员， 包括子宫红蛋白、Clara细胞10kD蛋白、小鼠雄激素结合 蛋白质和前列腺素。这些蛋白质产品已经被证明是 受类固醇调节，由上皮细胞分泌，起调节作用 炎症反应，或结合类固醇配体。假设是 测试表明，乳巨球蛋白对乳腺生物学是必不可少的，而且 乳房巨球蛋白的失调在某些乳房的病因中起一定作用 癌症。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.利用表位标记的巨球蛋白，鉴定 乳巨球蛋白复合体和确定乳巨球蛋白是否是类固醇 结合蛋白。2.检验乳头球蛋白表达的假设 对肿瘤表型有贡献。3.确定顺势作用的要素 赋予乳腺特异表达的启动子。4.确定 小鼠与乳大球蛋白的同源物；研究其在 发育中的胚胎，并启动研究以检查表型变化 巨噬细胞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.