The aim of our experiments is to understand the mechanism by which oncogenes, particularly the neu/Her-2 oncogene, cause specific cell-surface oligosaccharide changes in breast carcinoma cells and to determine if these changes affect cell adhesion properties. We and others have established that these oligosaccharide changes are caused by an increase in the activity of a particular glycosyltransferase, N-acetylglucosaminyltransferase V or GlcNAc-T V. The oligo-saccharide products of GlcNAc-T V have been shown to increase on the surfaces of fibroblasts and other cell types following oncogenic transformation. Moreover, the results of experiments from several laboratories suggest that alterations in the expression of these oligosaccharides influence the metastatic potential of cells. It is important, therefore, to understand in breast carcinomas how those oncogenes known to be associated with advanced breast cancer, such as neu/Her-2, alter GlcNAc-T V activity and there by its oligosaccharide products. We also wish to determine if these oligosaccharide changes have an effect on the intercellular adhesion of these cells. GlcNAc-T V, the enzyme responsible for synthesizing the critical surface oligosaccharide, has been cloned and transfected into a human carcinoma cell line resulting in increased amounts of oligo-N-acetyllactosamine in the cells and a more aggressive, cancer-like phenotype. An inducible plasmid has been constructed in which expression of GlcNAc-T V is under control of an unrelated inducer. Preliminary results with stable, inducible transformants resulting from this construct exhibit a fourfold increase in GlcNAc-T V activity following induction.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR005351-10
Application #
6122183
Study Section
Project Start
1998-09-30
Project End
1999-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Georgia
Department
Type
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602
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