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: 2449465
• 负责人: TIMOTHY Peter FLEMING
• 金额: $ 10.14万
• 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/2449465
• 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.

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