GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome.
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 concentration...
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2012
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oai:doaj.org-article:55417cbeeae3435aa60e10e4be6cdda62021-11-18T07:18:21ZGABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome.1932-620310.1371/journal.pone.0037041https://doaj.org/article/55417cbeeae3435aa60e10e4be6cdda62012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22615883/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203GABA (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.Anja SmitsZhe JinTamador ElsirHugo PedderMonica NistérIrina AlafuzoffAnna DimbergPer-Henrik EdqvistFredrik PonténEleonora AronicaBryndis BirnirPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37041 (2012) |
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Medicine R Science Q Anja Smits Zhe Jin Tamador Elsir Hugo Pedder Monica Nistér Irina Alafuzoff Anna Dimberg Per-Henrik Edqvist Fredrik Pontén Eleonora Aronica Bryndis Birnir GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome. |
| description |
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. |
| format |
article |
| author |
Anja Smits Zhe Jin Tamador Elsir Hugo Pedder Monica Nistér Irina Alafuzoff Anna Dimberg Per-Henrik Edqvist Fredrik Pontén Eleonora Aronica Bryndis Birnir |
| author_facet |
Anja Smits Zhe Jin Tamador Elsir Hugo Pedder Monica Nistér Irina Alafuzoff Anna Dimberg Per-Henrik Edqvist Fredrik Pontén Eleonora Aronica Bryndis Birnir |
| author_sort |
Anja Smits |
| title |
GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome. |
| title_short |
GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome. |
| title_full |
GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome. |
| title_fullStr |
GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome. |
| title_full_unstemmed |
GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome. |
| title_sort |
gaba-a channel subunit expression in human glioma correlates with tumor histology and clinical outcome. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/55417cbeeae3435aa60e10e4be6cdda6 |
| work_keys_str_mv |
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