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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA076227-03
Application #
6137633
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Freeman, Colette S
Project Start
1998-01-01
Project End
2001-12-31
Budget Start
2000-01-01
Budget End
2001-12-31
Support Year
3
Fiscal Year
2000
Total Cost
$130,976
Indirect Cost
Name
Washington University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Fanger, G R; Houghton, R L; Retter, M W et al. (2002) Detection of mammaglobin in the sera of patients with breast cancer. Tumour Biol 23:212-21
Carter, Darrick; Douglass, John F; Cornellison, Charisa D et al. (2002) Purification and characterization of the mammaglobin/lipophilin B complex, a promising diagnostic marker for breast cancer. Biochemistry 41:6714-22
Fleming, T P; Watson, M A (2000) Mammaglobin, a breast-specific gene, and its utility as a marker for breast cancer. Ann N Y Acad Sci 923:78-89
Watson, M A; Dintzis, S; Darrow, C M et al. (1999) Mammaglobin expression in primary, metastatic, and occult breast cancer. Cancer Res 59:3028-31
Becker, R M; Darrow, C; Zimonjic, D B et al. (1998) Identification of mammaglobin B, a novel member of the uteroglobin gene family. Genomics 54:70-8