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Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region

Deletion of 13q14.3 and a candidate gene KCNRG (potassium channel regulating gene) is the most frequent chromosomal abnormality in B-cell chronic lymphocytic leukemia and is a common finding in multiple myeloma (MM). KCNRG protein may interfere with the normal assembly of the K+ channel proteins cau...

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Autores principales: Birerdinc, Aybike, Nohelty, Elizabeth, Marakhonov, Andrey, Manyam, Ganiraju, Panov, Ivan, Coon, Stephanie, Nikitin, Eugene, Skoblov, Mikhail, Chandhoke, Vikas, Baranova, Ancha
Formato: Texto
Lenguaje:English
Publicado: Springer Netherlands 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803748/
https://www.ncbi.nlm.nih.gov/pubmed/20237900
http://dx.doi.org/10.1007/s13277-009-0005-0
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author Birerdinc, Aybike
Nohelty, Elizabeth
Marakhonov, Andrey
Manyam, Ganiraju
Panov, Ivan
Coon, Stephanie
Nikitin, Eugene
Skoblov, Mikhail
Chandhoke, Vikas
Baranova, Ancha
author_facet Birerdinc, Aybike
Nohelty, Elizabeth
Marakhonov, Andrey
Manyam, Ganiraju
Panov, Ivan
Coon, Stephanie
Nikitin, Eugene
Skoblov, Mikhail
Chandhoke, Vikas
Baranova, Ancha
author_sort Birerdinc, Aybike
collection PubMed
description Deletion of 13q14.3 and a candidate gene KCNRG (potassium channel regulating gene) is the most frequent chromosomal abnormality in B-cell chronic lymphocytic leukemia and is a common finding in multiple myeloma (MM). KCNRG protein may interfere with the normal assembly of the K+ channel proteins causing the suppression of Kv currents. We aimed to examine possible role of KCNRG haploinsufficiency in chronic lymphocytic leukemia (CLL) and MM cells. We performed detailed genomic analysis of the KCNRG locus; studied effects of the stable overexpression of KCNRG isoforms in RPMI-8226, HL-60, and LnCaP cells; and evaluated relative expression of its transcripts in various human lymphomas. Three MM cell lines and 35 CLL PBL samples were screened for KCNRG mutations. KCNRG exerts growth suppressive and pro-apoptotic effects in HL-60, LnCaP, and RPMI-8226 cells. Direct sequencing of KCNRG exons revealed point mutation delT in RPMI-8226 cell line. Levels of major isoform of KCNRG mRNA are lower in DLBL lymphomas compared to normal PBL samples, while levels of its minor mRNA are decreased across the broad range of the lymphoma types. The haploinsufficiency of KCNRG might be relevant to the progression of CLL and MM at least in a subset of patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13277-009-0005-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-28037482010-01-22 Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region Birerdinc, Aybike Nohelty, Elizabeth Marakhonov, Andrey Manyam, Ganiraju Panov, Ivan Coon, Stephanie Nikitin, Eugene Skoblov, Mikhail Chandhoke, Vikas Baranova, Ancha Tumour Biol Research Article Deletion of 13q14.3 and a candidate gene KCNRG (potassium channel regulating gene) is the most frequent chromosomal abnormality in B-cell chronic lymphocytic leukemia and is a common finding in multiple myeloma (MM). KCNRG protein may interfere with the normal assembly of the K+ channel proteins causing the suppression of Kv currents. We aimed to examine possible role of KCNRG haploinsufficiency in chronic lymphocytic leukemia (CLL) and MM cells. We performed detailed genomic analysis of the KCNRG locus; studied effects of the stable overexpression of KCNRG isoforms in RPMI-8226, HL-60, and LnCaP cells; and evaluated relative expression of its transcripts in various human lymphomas. Three MM cell lines and 35 CLL PBL samples were screened for KCNRG mutations. KCNRG exerts growth suppressive and pro-apoptotic effects in HL-60, LnCaP, and RPMI-8226 cells. Direct sequencing of KCNRG exons revealed point mutation delT in RPMI-8226 cell line. Levels of major isoform of KCNRG mRNA are lower in DLBL lymphomas compared to normal PBL samples, while levels of its minor mRNA are decreased across the broad range of the lymphoma types. The haploinsufficiency of KCNRG might be relevant to the progression of CLL and MM at least in a subset of patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13277-009-0005-0) contains supplementary material, which is available to authorized users. Springer Netherlands 2009-12-18 /pmc/articles/PMC2803748/ /pubmed/20237900 http://dx.doi.org/10.1007/s13277-009-0005-0 Text en © The Author(s) 2009 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Research Article
Birerdinc, Aybike
Nohelty, Elizabeth
Marakhonov, Andrey
Manyam, Ganiraju
Panov, Ivan
Coon, Stephanie
Nikitin, Eugene
Skoblov, Mikhail
Chandhoke, Vikas
Baranova, Ancha
Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region
title Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region
title_full Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region
title_fullStr Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region
title_full_unstemmed Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region
title_short Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region
title_sort pro-apoptotic and antiproliferative activity of human kcnrg, a putative tumor suppressor in 13q14 region
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803748/
https://www.ncbi.nlm.nih.gov/pubmed/20237900
http://dx.doi.org/10.1007/s13277-009-0005-0
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