Date of Award
Bachelor of Science
Valerie M. Kish, Ph.D.
Glioblastoma multiforme (GBM), a high-grade, malignant brain tumor of astrocyte origin, invades normal brain tissue and most often results in death ofthe patient withinayearofdiagnosis. In order to invade the surrounding tissue and thereby metastasize, these tumor cells must migrate through the extracellular matrix. The pmpose ofthis research project is to investigate the family ofmatrix metalloproteinases responsible for extracellular degradation. Specifically, this investigation looks at MMP-2 activation via MT 1-MMP and the possible importance of phosphorylation of the tyrosine residue on the cytoplasmic tail of MTl-MMP. U87wildtypegliomacellsaswellasT98 p53 mutant glioma cells were treated with transforming growth factor beta (TGF-P). Preliminary results indicate a lesser concentration of MTl-MMP and a greater concentration of phosphorylated tyrosine (P-Tyr) in the treated U87 cells. Similar experiments with T98 cells indicate a lesser concentration of MTl-MMP in the treated samples and no effect on the phosphorylation of tyrosine. Results withTGF-P-treated T98 cells imply that TGF-P does not upregulate MTl-MMPproduction. U87 cells were also treated with epidermal growth factor (EGF). Results indicate a greater concentration of MTl-MMP as well as a greater concentration of phosphorylated tyrosine in the EGF treated conditions. Zymography results shows no effect ofEGF treatment on MMP-2 production. While TGF-P has not been found to up regulate MTl-MMP productionin either U87 or T98 cells, results do indicate that EGF upregulates MTl-MMP as well as phosphorylation of the tyrosine residue in U87 cells.
Knupp, Jacquelyn B., "The effect of TGF-B and EGF on MMP-2 activation and MT1-MMP phosphorylation in U87MG and T98G human glioma cells" (2006). Honors Theses. 1067.