2 research outputs found
Immunoexpression patterns for Hypoxia-inducible Factor-1α and von Hippel-Lindau protein, in relation to Hsp90, of human brain tumors
The pathogenesis of many tumors, including
brain tumors, has been associated with hypoxia, which
induces the transcriptional activity of Ηypoxia-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 HIF1α/pVHL/Hsp90 interactions may be implicated in
biology of different types of brain tumors through
different signaling mechanisms