The malignant phenotype, by definition, is composed of two facets, consisting of the tumor's ability to proliferate as well as its ability to invade the surrounding normal tissue. We propose that in malignant gliomas the protein kinase C (PKC) family of enzymes, which has been shown to be overexpressed in these tumours, plays a pivotal role in both their proliferative and invasive capacity. In the first genes of experiments where the expression of the alpha isoform of PKC was significantly decreased following antisense oligonucleotide treatment, we were able to report the novel finding that this inhibition not only inhibits glioma proliferation in a dose-dependent manner but that this inhibition of growth was the consequence of programmed cell death (1). In the second focus of this thesis, we addressed the postulate that the high PKC activity present in glioblastoma cells may also contribute to the invasive nature of this tumor by modulating the expression of proteolytic enzymes, the matrix metalloproteinases, (MMPs). In contrast to previous studies implicating MMP-9, our data demonstrated that MMP-2 was the metalloproteinase most closely associated with glioma invasion. Furthermore, we were also able to report that the regulation of MMP-2, and thus glioma invasion, could be modulated by PKC (2). In summary, this work presents evidence to support a role for PKC in both the proliferative and invasive phenotypes which characterize malignant gliomas. The translational nature of this research is readily illustrated by the emergence of clinical trials in which PKC and MMPs constitute the principal chemotherapeutic targets.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35694 |
| Date | January 1998 |
| Creators | Dooley, Nora P. |
| Contributors | Yong, Voon Wee (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Neurology and Neurosurgery.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001650434, proquestno: NQ50149, Theses scanned by UMI/ProQuest. |
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