Date of Award

2006

Document Type

Thesis

Department

Biology

First Advisor

Dr. Valerie M. Kish

Abstract

The effects of epidermal growth factor (EGF) on proteins that have been implicated in the migration of the Grade IV brain tumor, glioblastoma multiforme, were investigated in this study. Differential expression levels of TIMP-2, MMP-2, and MT1-MMP in response to EGF treatment were compared by immunoprecipitation, and immunoblotting. This study involved two different cultured glioma cell lines, U87, which expresses wild-type p53, and T98, which has a mutation in the p53 gene, in order to determine if the status of the p53 tumor suppression gene is a factor in the regulation of proteins involved in this migration pathway. It was determined that the only response of mutant cells to EGF treatment was the putative upregulation of the level of TIMP-2 protein. Treatment of the U87 cells resulted in increased phosphorylation of MTl-MMP. It was believed that phosphorylation of MT1-MMP correlated with activity and ability to cleave the proenzyme of MMP-2, however, the level of MMP-2 activity actually decreased. These data highlight the complex interaction of p53 status and protein expression and activation that corresponds to the ability of tumor cells to migrate.

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