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Date of Award

4-2003

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Valerie M. Kish

Abstract

Patients diagnosed with a high-grade glioma often receive a poor prognosis due to the lethal invasiveness of this form of brain cancer. Knowledge of the specific cellular mechanisms underlying glioma invasion is relatively incomplete, yet is essential to successfully treat this cancer. The invasive capabilities of certain glioma cell lines have been linked to the enzymatic activity of the matrix metalloproteinases (MMPs), a family of proteins. The signaling pathway that regulates the production and activity of these enzymes is uncertain, however there is evidence that the EGF/EGFR complex may play a role. Preliminary findings suggest that the epidermal growth factor (EGF) binds to its receptor (EGFR) on the cancerous cell's surface initiating a cascade of signaling pathways, one of which leads to the production of MMP-2 and MMP-9 proteins. The plant lectin Concanavalin A (ConA) has demonstrated similar stimulatory effects on the synthesis of MMP proteins in glioma cell lines. Once produced, MMPs are secreted from the cell and degrade the surrounding extracellular matrix, thereby allowing for invasion of the surrounding tissues. We have examined the effect of EGF and ConA on levels of MMP-2 and MMP-9 activity using a p53-mutant human glioma cell. p53, a tumor suppressor protein, acts as a transcription factor for the MMP-2 gene. Our results indicate that the overall production and secretion of MMP-2 and MMP-9 increase with increasing EGF and ConA concentrations. However, this increase is not specific to the MMP proteins. Instead, EGF and ConA seem to have a generalized mitogenic function, which increases overall protein production in this p53-mutant glial cell line. Therefore, wild-type p53 may be necessary for the targeted induction of MMP-2 and MMP-9 by EGF.

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