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GABA-A Channel Subunit Expression in Human Glioma Correlates with Tumor Histology and Clinical Outcome
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- Smits, Anja (författare)
- Uppsala universitet,Neurologi
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- Jin, Zhe (författare)
- Uppsala universitet,Fysiologi
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- Elsir, Tamador (författare)
- Uppsala universitet,Neurologi
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- Aronica, Eleonora (författare)
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- (creator_code:org_t)
- 2012-05-17
- 2012
- Engelska.
- Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5, s. e37041-
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the CNS and is present in high concentrations in presynaptic terminals of neuronal cells. More recently, GABA has been ascribed a more widespread role in the control of cell proliferation during development where low concentrations of extrasynaptic GABA induce a tonic activation of GABA receptors. The GABA-A receptor consists of a ligand-gated chloride channel, formed by five subunits that are selected from 19 different subunit isoforms. The functional and pharmacological properties of the GABA-A channels are dictated by their subunit composition. Here we used qRT-PCR to compare mRNA levels of all 19 GABA-A channel subunits in samples of human glioma (n = 29) and peri-tumoral tissue (n = 5). All subunits except the ρ1 and ρ3 subunit were consistently detected. Lowest mRNA levels were found in glioblastoma compared to gliomas of lower malignancy, except for the θ subunit. The expression and cellular distribution of the α1, γ1, ρ2 and θ subunit proteins was investigated by immunohistochemistry on tissue microarrays containing 87 gliomas grade II. We found a strong co-expression of ρ2 and θ subunits in both astrocytomas (r = 0.86, p<0.0001) and oligodendroglial tumors (r = 0.66, p<0.0001). Kaplan-Meier analysis and Cox proportional hazards modeling to estimate the impact of GABA-A channel subunit expression on survival identified the ρ2 subunit (p = 0.043) but not the θ subunit (p = 0.64) as an independent predictor of improved survival in astrocytomas, together with established prognostic factors. Our data give support for the presence of distinct GABA-A channel subtypes in gliomas and provide the first link between specific composition of the A-channel and patient survival.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Neurology
- Neurologi
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- Smits, Anja
- Jin, Zhe
- Elsir, Tamador
- Pedder, Hugo
- Nistér, Monica
- Alafuzoff, Irina
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- Dimberg, Anna
- Edqvist, Per-Hen ...
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