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Author

Megan Cox

Date of Award

Fall 2004

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Valerie Kish

Abstract

Glioblastoma multiforme, a highly invasive human brain tumor, is unique because of its high rate of metastasis. The progression of this tumor is attributed to the presence of transforming growth factor beta (TGF-Beta) because of its ability to stimulate the migration of glioma cells. These tumors are accompanied by high levels of matrix metalloproteinase 2 (MMP2). This enzyme is secreted from the cell as a proenzyme and activated by the autocatalysis of theN-terminal domain, which produces an active MMP2 enzyme. Another matrix metalloproteinase that is recognized in the progression of this tumor is membrane type 1-MMP (MTI-MMP). Two molecules ofMTl-MMP are coupled with one molecule of tissue inhibitor of metalloproteinases (TIMP2) to form a cleavage complex involved in the activation ofMMP2. MTl-MMP is composed of a hydrophobic transmembrane domain and a short cytoplasmic tail that has three potential phosphorylation sites for tyrosine, threonine, and serine. We hypothesize that the degree of phosphorylation ofMTl-MMP affects its cellular function. To investigate the effect of the phosphorylation ofMTl-MMP on the activation ofMMP2, a U87 glioma cell line derived initially from a glioblastoma multiforme tumor was treated with TGF-Beta. Western Blots were then performed to evaluate the presence ofMTI-MMP and its phosphorylation. Activity ofMMP2 was also analyzed using zymography. Our results have shown an increase in MTI-MMP levels when treated with TGF-Beta.

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