This application is being submitted in response to PA-01010, Exploratory Studies in Cancer Detection, Prognosis, and Prediction. The overall goal of this project will be to analyze the expression pattern and structure of a novel breast biomarker, designated Small Breast Epithelial Mucin (SBEM), and to use this information for the development of a predictive or diagnostic test for breast cancer. Preliminary observations indicate that SBEM is preferentially expressed and presumably secreted by adult non-lactating mammary gland, breast tumor cell lines, and by primary breast adenocarcinomas. We therefore hypothesize that SBEM may represent a promising serum marker for breast cancer. Project aims include the use of lectin affinity chromatography to purify SBEM protein from breast tumor cell lines and normal breast epithelial cells, to characterize the structure of SBEM focusing on differences in glycosylation between normal and malignant cells, and to generate SBEM-specific monoclonal antibodies. To facilitate these aims and to explore the potential of using SBEM as the basis for a breast tumor vaccine, work will be conducted in parallel to engineer several SBEM expression systems including vaccinia viral vectors and the development of cell lines that stably over express both secreted and cell surface forms of this breast-specific mucin. A supplementary aim will entail comparison of the copy number of the SBEM gene with nearby genes in the Os9 / MDM2 amplicon at 12q13-q15 in breast tumor cell lines. Finally, the regulatory region upstream of the SBEM gene will be cloned and characterized with respect to its ability to support breast epithelial cell-specific transcription in transfected cell lines. Defining gene regulatory sequences capable of narrowly targeting gene transcription to the mammary epithelium would be highly beneficial for future projects employing gene therapy to treat breast cancer. Accomplishing these aims should facilitate the development of a serum test for breast cancer intended to complement screening mammography for the early detection of breast tumors. Such a test might also prove useful for the diagnostic evaluation of suspicious mammographic lesions and as a clinical benchmark during the treatment of breast cancer, similar to the use of Prostate Specific Antigen (PSA) in the management of prostate cancer. A longer-term goal entails the development of an SBEM-based vaccine for the treatment and conceivably the prevention of breast cancer.
| Miksicek, Richard J; Myal, Yvonne; Watson, Peter H et al. (2002) Identification of a novel breast- and salivary gland-specific, mucin-like gene strongly expressed in normal and tumor human mammary epithelium. Cancer Res 62:2736-40 |
