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  • Smits, AnjaUppsala universitet,Neurologi (author)

GABA-A Channel Subunit Expression in Human Glioma Correlates with Tumor Histology and Clinical Outcome

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012-05-17
  • Public Library of Science (PLoS),2012
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-175309
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-175309URI
  • https://doi.org/10.1371/journal.pone.0037041DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:124815072URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Jin, ZheUppsala universitet,Fysiologi(Swepub:uu)zheji315 (author)
  • Elsir, TamadorUppsala universitet,Neurologi(Swepub:uu)elsta774 (author)
  • Pedder, HugoUppsala universitet,Neurologi (author)
  • Nistér, MonicaKarolinska Institutet (author)
  • Alafuzoff, IrinaUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)irial548 (author)
  • Dimberg, AnnaUppsala universitet,Cancer och vaskulärbiologi(Swepub:uu)annadimb (author)
  • Edqvist, Per-HenrikUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)peedq227 (author)
  • Pontén, FredrikUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)fredpont (author)
  • Aronica, Eleonora (author)
  • Birnir, BryndisUppsala universitet,Fysiologi(Swepub:uu)brybi979 (author)
  • Uppsala universitetNeurologi (creator_code:org_t)

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  • In:PLOS ONE: Public Library of Science (PLoS)7:5, s. e37041-1932-6203

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