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Author

Amorette Rofe

Date of Award

4-25-2003

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Valerie Kish

Abstract

It has been found that natural green tea catechins, especially epigallocatechin gallate (EGCG) can inhibit cancer by reducing mutagenesis, tumorigenesis, angiogenesis, tumor growth, invasion, and metastasis. We are interested in evaluating the mechanism by which this occurs using a brain cancer model system. Glioblastoma multiforme invades surrounding brain tissue by degrading the extracellular matrix. Two matrixmetalloproteinases involved with this process are MT1-MMP and MMP-2. MMP-2 is a soluble protein produced by the cell that can cleave the extracellular matrix (ECM) surrounding nearby cells. However, it is secreted in an inactive form, pro-MMP-2. Cellular membrane attached MT1-MMP can cleave pro-MMP-2 when it is complexed with an activator/inhibitor, TIMP-2. The activation of MT1-MMP may involve the phosphorylation of one of three amino acids in the cytoplasmic tail, one of which is tyrosine residue 573. We investigated the effect of EGCG on MMP-2 activity, since this protein is involved in tumor cell invasion. Our data indicates that EGCG decreases MMP-2 activity, thereby supporting the inhibitory effect of this compound on tumor cells. MT1-MMP expression and tyrosine phosphorylation levels are not altered in the presence of EGCG. However, MMP-2 protein levels in the conditioned media decreased when the cells were treated with EGCG. Therefore, EGCG inhibits the activity of MMP- 2 by decreasing the amount of MMP-2 secreted out of the cell. This ultimately may lead to a possible decrease in the degradation of the ECM and a decrease in metastasis of the tumor cells.

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