title: Immunoexpression patterns for Hypoxia-inducible Factor-1α and von Hippel-Lindau protein, in relation to Hsp90, of human brain tumors.
abstract: The pathogenesis of many tumors, including brain tumors, has been associated with hypoxia, which induces the transcriptional activity of hypoxia-inducible Factor-1α (HIF-1α). HIF-1α is normally degradated by the von Hippel-Lindau protein (pVHL) but, in hypoxia, pVHL/HIF-1α interaction is inhibited resulting in the nuclear accumulation of HIF-1α. Hsp90 (Heat shock protein 90), as a chaperone protein, plays a critical role for both stabilization of HIF-1α and degradation of pVHL. The aim of this study was to estimate immunohistochemically the expression levels of HIF-1α and pVHL, in relation to Hsp90, in different types of human brain tumors (42 gliomas, 9 medulloblastomas, and 38 meningiomas) using specific antibodies. The tumors were further divided into two groups according to the age of patients (≥19 years old or ⟨19 years old). Nuclear, for HIF-1α, and cytoplasmic, for pVHL and Hsp90, localization was detected in a high percentage of tumor cells in the majority of tumors. In astrocytomas, a significant, grade-dependent relationship for HIF-1α immunoexpression was observed (p⟨0.05). Furthermore, there was a significant correlation between pVHL and Hsp90 immunoexpression (p⟨0.01). The group of ≥19 years old patients with glioblastomas (WHO grade IV) demonstrated significantly increased immunoexpression for HIF-1α compared to pVHL (p⟨0.0001) and Hsp90 expression (p⟨0.01). In medulloblastomas, a significant correlation of HIF-1α with Hsp90 immunoexpression (p⟨0.05) was found. In meningiomas, no significant correlation for the expression of the three proteins was detected (p≥0.05). These results indicate that HIF-1α/pVHL/Hsp90 interactions may be implicated in biology of different types of brain tumors through different signaling mechanisms.
authors.affiliation: Department of Anatomy-Histology and Embryology, School of Medicine, University of Patras, Rion, Greece. massim@upatras.gr.
authors.forename: Martha
authors.initials: M
authors.lastname: Assimakopoulou
authors.affiliation: Department of Anatomy-Histology and Embryology, School of Medicine, University of Patras, Rion, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Androutsopoulou
authors.affiliation: Department of Pathology, School of Medicine, University of Patras, Rion, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Zolota
authors.affiliation: Department of Chemistry, School of Natural Sciences, University of Patras, Rion, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Matsoukas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000032:analysis / Q000378:metabolism*; D055815:Young Adult
chemical_list: C497442:HIF1A protein, human; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human