title: Hypoxia-inducible factor-1 and associated upstream and downstream proteins in the pathophysiology and management of glioblastoma.
abstract: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an exceptionally poor patient outcome despite aggressive therapy including surgery, radiation, and chemotherapy. This aggressive phenotype may be associated with intratumoral hypoxia, which probably plays a key role in GBM tumor growth, development, and angiogenesis. A key regulator of cellular response to hypoxia is the protein hypoxia-inducible factor–1 (HIF-1). An examination of upstream hypoxic and nonhypoxic regulation of HIF-1 as well as a review of the downstream HIF-1– regulated proteins may provide further insight into the role of this transcription factor in GBM pathophysiology. Recent insights into upstream regulators that intimately interact with HIF-1 could provide potential therapeutic targets for treatment of this tumor. The same is potentially true for HIF-1–mediated pathways of glycolysis-, angiogenesis-, and invasion-promoting proteins. Thus, an understanding of the relationship between HIF-1, its upstream protein regulators, and its downstream transcribed genes in GBM pathogenesis could provide future treatment options for the care of patients with these tumors.
authors.forename: Matthew
authors.initials: M
authors.lastname: Womeldorff
authors.forename: David
authors.initials: D
authors.lastname: Gillespie
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jensen
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D005909:Glioblastoma / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008958:Models, Molecular; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051793:Hypoxia-Inducible Factor 1