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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| Veröffentlicht in: | PloS one 2012-05, Vol.7 (5), p.e37041-e37041 |
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| creator | Smits, Anja Jin, Zhe Elsir, Tamador Pedder, Hugo Nistér, Monica Alafuzoff, Irina Dimberg, Anna Edqvist, Per-Henrik Pontén, Fredrik Aronica, Eleonora Birnir, Bryndis |
| 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 |
| doi_str_mv | 10.1371/journal.pone.0037041 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0037041</identifier><identifier>PMID: 22615883</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Astrocytoma ; Biology ; Brain cancer ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Brain tumors ; Cell proliferation ; Central nervous system ; Chloride Channels - genetics ; Chloride Channels - metabolism ; Clinical outcomes ; Development and progression ; Female ; GABA ; gamma-Aminobutyric Acid - biosynthesis ; gamma-Aminobutyric Acid - genetics ; Genetics ; Glioblastoma ; Glioma ; Glioma - genetics ; Glioma - metabolism ; Glioma - pathology ; Hazards ; Histology ; Humans ; Immunohistochemistry ; Immunology ; Ionizing radiation ; Isoforms ; Kaplan-Meier Estimate ; Low concentrations ; Male ; Malignancy ; Medical prognosis ; Medicin och hälsovetenskap ; Medicine ; mRNA ; Mutation ; Neoplasm Staging ; Neurologi ; Neurology ; Neurons ; Neurosciences ; Pathology ; Patient outcomes ; Pharmacology ; Physical properties ; Physiology ; Prognosis ; Protein expression ; Protein Isoforms ; Protein Subunits ; Proteins ; Proteomics ; Receptors ; Receptors, GABA - biosynthesis ; Receptors, GABA - genetics ; Retrospective Studies ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Stem cells ; Subunit structure ; Survival ; Survival Rate ; Trends ; Tumors ; γ-Aminobutyric acid A receptors ; γ-Aminobutyric acid receptors</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e37041-e37041</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Smits et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Smits et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c817t-ff60d12a8433bd24cba2aa3c9681e067e1af09ea6f814c90bdb9191f73766b643</citedby><cites>FETCH-LOGICAL-c817t-ff60d12a8433bd24cba2aa3c9681e067e1af09ea6f814c90bdb9191f73766b643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355166/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355166/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,552,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22615883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-175309$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:124815072$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Lesniak, Maciej S.</contributor><creatorcontrib>Smits, Anja</creatorcontrib><creatorcontrib>Jin, Zhe</creatorcontrib><creatorcontrib>Elsir, Tamador</creatorcontrib><creatorcontrib>Pedder, Hugo</creatorcontrib><creatorcontrib>Nistér, Monica</creatorcontrib><creatorcontrib>Alafuzoff, Irina</creatorcontrib><creatorcontrib>Dimberg, Anna</creatorcontrib><creatorcontrib>Edqvist, Per-Henrik</creatorcontrib><creatorcontrib>Pontén, Fredrik</creatorcontrib><creatorcontrib>Aronica, Eleonora</creatorcontrib><creatorcontrib>Birnir, Bryndis</creatorcontrib><title>GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Adult</subject><subject>Astrocytoma</subject><subject>Biology</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain tumors</subject><subject>Cell proliferation</subject><subject>Central nervous system</subject><subject>Chloride Channels - genetics</subject><subject>Chloride Channels - metabolism</subject><subject>Clinical outcomes</subject><subject>Development and progression</subject><subject>Female</subject><subject>GABA</subject><subject>gamma-Aminobutyric Acid - biosynthesis</subject><subject>gamma-Aminobutyric Acid - genetics</subject><subject>Genetics</subject><subject>Glioblastoma</subject><subject>Glioma</subject><subject>Glioma - genetics</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Hazards</subject><subject>Histology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Ionizing radiation</subject><subject>Isoforms</subject><subject>Kaplan-Meier Estimate</subject><subject>Low concentrations</subject><subject>Male</subject><subject>Malignancy</subject><subject>Medical prognosis</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>mRNA</subject><subject>Mutation</subject><subject>Neoplasm Staging</subject><subject>Neurologi</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurosciences</subject><subject>Pathology</subject><subject>Patient outcomes</subject><subject>Pharmacology</subject><subject>Physical properties</subject><subject>Physiology</subject><subject>Prognosis</subject><subject>Protein expression</subject><subject>Protein Isoforms</subject><subject>Protein Subunits</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Receptors</subject><subject>Receptors, GABA - biosynthesis</subject><subject>Receptors, GABA - genetics</subject><subject>Retrospective Studies</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Stem cells</subject><subject>Subunit structure</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Trends</subject><subject>Tumors</subject><subject>γ-Aminobutyric acid A receptors</subject><subject>γ-Aminobutyric acid receptors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNqNk21r1TAYhosobk7_gWhhIAqeY9K0SftFOE6dg8HAl30Nafr0nMw0OebFbf_enJ1urrKB5EPD0-u-k9zJk2XPMZpjwvC7MxudEXq-tgbmCBGGSvwg28UNKWa0QOThrflO9sT7M4QqUlP6ONspCoqruia7WX-4-LCYLXK5EsaAzn1so1Ehh4u1A--VNbky-SoOwuRLrewgcmmdAy0C-PxchVUe4mBdvlI-WG2Xl7kwXS61MkoKndsYpB3gafaoF9rDs_G7l_34_On7wZfZ8cnh0cHieCZrzMKs7ynqcCHqkpC2K0rZikIIIhtaY0CUARY9akDQvsalbFDbtQ1ucM8Io7SlJdnLXm5919p6PkbkOSZFSVFTsyYRR1uis-KMr50ahLvkVih-VbBuyYULSmrgVVViJlsAAaQklRAUAUZQtkBl1wmavGZbL38O69hO3MbSzzRLToQ2rE58cy-_drb7K7oW4qKscYVYkbRv79V-VKeLq53HyDGrCNoc8_0YRGwH6CSY4ISerjj5Y9SKL-1vTkhVYbo52-vRwNlfEXzgg_IStBYGbEyRIlyVND2wzdb2_0HvDn6kliJlq0xv07pyY8oXJWOIlbRCiZrfQaXRwaBkeuq9SvWJ4M1EkJgAF2Epovf86NvX_2dPTqfsq1vsCoQOK291DKkl_BQst6B01nsH_U3IGPFNp16nwTedysdOTbIXty_oRnTdmuQP2Z47Ng</recordid><startdate>20120517</startdate><enddate>20120517</enddate><creator>Smits, Anja</creator><creator>Jin, Zhe</creator><creator>Elsir, Tamador</creator><creator>Pedder, Hugo</creator><creator>Nistér, Monica</creator><creator>Alafuzoff, Irina</creator><creator>Dimberg, Anna</creator><creator>Edqvist, Per-Henrik</creator><creator>Pontén, Fredrik</creator><creator>Aronica, Eleonora</creator><creator>Birnir, Bryndis</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ACNBI</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>DF2</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20120517</creationdate><title>GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome</title><author>Smits, Anja ; Jin, Zhe ; Elsir, Tamador ; Pedder, Hugo ; Nistér, Monica ; Alafuzoff, Irina ; Dimberg, Anna ; Edqvist, Per-Henrik ; Pontén, Fredrik ; Aronica, Eleonora ; Birnir, Bryndis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c817t-ff60d12a8433bd24cba2aa3c9681e067e1af09ea6f814c90bdb9191f73766b643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Astrocytoma</topic><topic>Biology</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain tumors</topic><topic>Cell proliferation</topic><topic>Central nervous system</topic><topic>Chloride Channels - genetics</topic><topic>Chloride Channels - metabolism</topic><topic>Clinical outcomes</topic><topic>Development and progression</topic><topic>Female</topic><topic>GABA</topic><topic>gamma-Aminobutyric Acid - biosynthesis</topic><topic>gamma-Aminobutyric Acid - genetics</topic><topic>Genetics</topic><topic>Glioblastoma</topic><topic>Glioma</topic><topic>Glioma - genetics</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Hazards</topic><topic>Histology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Ionizing radiation</topic><topic>Isoforms</topic><topic>Kaplan-Meier Estimate</topic><topic>Low concentrations</topic><topic>Male</topic><topic>Malignancy</topic><topic>Medical prognosis</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine</topic><topic>mRNA</topic><topic>Mutation</topic><topic>Neoplasm Staging</topic><topic>Neurologi</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Neurosciences</topic><topic>Pathology</topic><topic>Patient outcomes</topic><topic>Pharmacology</topic><topic>Physical properties</topic><topic>Physiology</topic><topic>Prognosis</topic><topic>Protein expression</topic><topic>Protein Isoforms</topic><topic>Protein Subunits</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Receptors</topic><topic>Receptors, GABA - biosynthesis</topic><topic>Receptors, GABA - genetics</topic><topic>Retrospective Studies</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Stem cells</topic><topic>Subunit structure</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Trends</topic><topic>Tumors</topic><topic>γ-Aminobutyric acid A receptors</topic><topic>γ-Aminobutyric acid receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smits, Anja</creatorcontrib><creatorcontrib>Jin, Zhe</creatorcontrib><creatorcontrib>Elsir, Tamador</creatorcontrib><creatorcontrib>Pedder, Hugo</creatorcontrib><creatorcontrib>Nistér, Monica</creatorcontrib><creatorcontrib>Alafuzoff, Irina</creatorcontrib><creatorcontrib>Dimberg, Anna</creatorcontrib><creatorcontrib>Edqvist, Per-Henrik</creatorcontrib><creatorcontrib>Pontén, Fredrik</creatorcontrib><creatorcontrib>Aronica, Eleonora</creatorcontrib><creatorcontrib>Birnir, Bryndis</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Uppsala universitet full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Uppsala universitet</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smits, Anja</au><au>Jin, Zhe</au><au>Elsir, Tamador</au><au>Pedder, Hugo</au><au>Nistér, Monica</au><au>Alafuzoff, Irina</au><au>Dimberg, Anna</au><au>Edqvist, Per-Henrik</au><au>Pontén, Fredrik</au><au>Aronica, Eleonora</au><au>Birnir, Bryndis</au><au>Lesniak, Maciej S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-05-17</date><risdate>2012</risdate><volume>7</volume><issue>5</issue><spage>e37041</spage><epage>e37041</epage><pages>e37041-e37041</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22615883</pmid><doi>10.1371/journal.pone.0037041</doi><tpages>e37041</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-05, Vol.7 (5), p.e37041-e37041 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1324609879 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; SWEPUB Freely available online; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Astrocytoma Biology Brain cancer Brain Neoplasms - genetics Brain Neoplasms - metabolism Brain Neoplasms - pathology Brain tumors Cell proliferation Central nervous system Chloride Channels - genetics Chloride Channels - metabolism Clinical outcomes Development and progression Female GABA gamma-Aminobutyric Acid - biosynthesis gamma-Aminobutyric Acid - genetics Genetics Glioblastoma Glioma Glioma - genetics Glioma - metabolism Glioma - pathology Hazards Histology Humans Immunohistochemistry Immunology Ionizing radiation Isoforms Kaplan-Meier Estimate Low concentrations Male Malignancy Medical prognosis Medicin och hälsovetenskap Medicine mRNA Mutation Neoplasm Staging Neurologi Neurology Neurons Neurosciences Pathology Patient outcomes Pharmacology Physical properties Physiology Prognosis Protein expression Protein Isoforms Protein Subunits Proteins Proteomics Receptors Receptors, GABA - biosynthesis Receptors, GABA - genetics Retrospective Studies RNA RNA, Messenger - genetics RNA, Messenger - metabolism Stem cells Subunit structure Survival Survival Rate Trends Tumors γ-Aminobutyric acid A receptors γ-Aminobutyric acid receptors |
| title | GABA-A channel subunit expression in human glioma correlates with tumor histology and clinical outcome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T09%3A47%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=GABA-A%20channel%20subunit%20expression%20in%20human%20glioma%20correlates%20with%20tumor%20histology%20and%20clinical%20outcome&rft.jtitle=PloS%20one&rft.au=Smits,%20Anja&rft.date=2012-05-17&rft.volume=7&rft.issue=5&rft.spage=e37041&rft.epage=e37041&rft.pages=e37041-e37041&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0037041&rft_dat=%3Cgale_plos_%3EA477074650%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1324609879&rft_id=info:pmid/22615883&rft_galeid=A477074650&rft_doaj_id=oai_doaj_org_article_55417cbeeae3435aa60e10e4be6cdda6&rfr_iscdi=true |