University of Texas Health Science Center at Houston
Epidermal Growth Factor Receptor Induces Fyn Expression Via Up-Regulation of P47Phox In Glioblastoma Multiforme
Abstract
dc:description.abstract<p>Src family kinases (SFKs) are commonly over-expressed and/or activated in glioblastoma multiforme (GBM), where they serve as key mediators of GBM cell proliferation, survival, invasion and angiogenesis. Mechanisms of allosteric SFK activation are well described; however, the SFK Fyn is commonly up-regulated at the mRNA level in multiple human cancers, including GBM, where the mode of increased expression is poorly understood. Since activating mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in GBM, we examined whether EGFR could induce Fyn expression. Here, we found that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants, EGFRΔIII and R108K, induce a substantial up-regulation of Fyn expression. Furthermore, it was determined that Fyn expression is up-regulated across a panel of patient-derived GBM stem cells (GSCs) relative to normal progenitor controls. Inhibition of Fyn proved to be biologically relevant, as Fyn depletion significantly (<em>p</em>p</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (PhD)
- Level thesis:degree_level
- Dissertation (PhD)
- Year dc:date.available
- 2014
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Johnson, Blake P
- Contributors dc:contributor
-
- Joya Chandra, Ph.D.
- Gary Gallick, Ph.D.
- Candelaria Gomez-Manzano, M.D.
Subjects
dc:subject × 3Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.library.tmc.edu/utgsbs_dissertations/539
- OAI identifier oai:identifier
- oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1577