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Date of Award

4-25-2003

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Valerie M Kish

Abstract

Matrix metalloproteinases (MMPs) are important proteolytic enzymes involved in cancer-cell growth, migration, invasion, metastasis, and angiogenesis. MMPs are upregulated in almost every type of human cancer and their expression is often associated with poor survival. One pathway in which MMPs are activated is thought to be induced by the presence of epidermal growth factor (EGF). Upon initiation of the pathway, a cascade of reactions leads to the ultimate activation of membrane type-1 matrix metalloproteinases (MT-1 MMP) through the phosphorylation of one of its amino acid residues, which in tum activate the secreted soluble MMP molecules (MMP-2 and MMP- 9) that propagate extracellular matrix (ECM) degradation. The focus of our research is to determine the effect of EGF on the phosphorylation of MT-1 MMP. The structure of MT-1 MMP contains both transmembrane and cytoplasmic domains. There are three possible phosphorylation sites on the cytoplasmic domain, more specifically serine577, tyrosine573 , and threonine567 • The serine577 residue is thought not to be involved (Lehti et al., 2000). Previous work of our research group has shown tyrosine phosphorylation is involved with MT-1 MMP activation (K. Lewis, Honors Thesis). Our goal is to determine if threonine phosphorylation is another regulatory mechanism associated with MT-1 MMP. We used the U87 human glioma cell line, which is wild-type for p53 (a tumor suppressor gene), and the techniques ofimmunocapture, SDS-PAGE, and western blot analysis. The data shows that MT-1 MMP does contain phoshphorylated threonine, but we cannot conclusively say that it is at threonine567. There seems to be no correlation between the presence of EGF and MT-1 MMP expression or threonine phosphorylation.

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