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Date of Award

Spring 2006

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Valerie M. Kish

Abstract

Gliomas are among the most common human brain tumors, and they are associated with high invasiveness and poor prognoses; glioblastoma multiforme (GBM) is the most severe of these. Heat shock protein 27, a molecular chaperone up-regulated in response to environmental stress, has been implicated in the regulation of the actin cytoskeleton and may be involved in tumor metastasis. Matrix metalloproteinase 2, a zinc-dependent endopeptidase that cleaves components of the extracellular matrix, has also been shown to have involvement in tumor cell migration. We have observed that HSP27 is up-regulated and the secretion and activation of MMP2 is increased in response to heat shock treatment. Because of each of these protein's possible role in affecting tumor metastasis, we investigated the possibility of a more direct relationship between them. We heat shocked U87 glioma cells in the presence of SB203580, a p38 kinase inhibitor, which prevented HSP27 phosphorylation and activation. Western blotting and zymography showed that both intracellular HSP27 and extracellular active MMP2 levels were not increased following heat shock and inhibitor treatment, which suggests that active HSP27 may be partially responsible for regulating MMP2 secretion and/or activation.

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