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Frequent down-regulation of ABC transporter genes in prostate cancer

BACKGROUND: ATP-binding cassette (ABC) transporters are transmembrane proteins responsible for the efflux of a wide variety of substrates, including steroid metabolites, through the cellular membranes. For better characterization of the role of ABC transporters in prostate cancer (PCa) development,...

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Autores principales: Demidenko, Rita, Razanauskas, Deividas, Daniunaite, Kristina, Lazutka, Juozas Rimantas, Jankevicius, Feliksas, Jarmalaite, Sonata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603841/
https://www.ncbi.nlm.nih.gov/pubmed/26459268
http://dx.doi.org/10.1186/s12885-015-1689-8
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author Demidenko, Rita
Razanauskas, Deividas
Daniunaite, Kristina
Lazutka, Juozas Rimantas
Jankevicius, Feliksas
Jarmalaite, Sonata
author_facet Demidenko, Rita
Razanauskas, Deividas
Daniunaite, Kristina
Lazutka, Juozas Rimantas
Jankevicius, Feliksas
Jarmalaite, Sonata
author_sort Demidenko, Rita
collection PubMed
description BACKGROUND: ATP-binding cassette (ABC) transporters are transmembrane proteins responsible for the efflux of a wide variety of substrates, including steroid metabolites, through the cellular membranes. For better characterization of the role of ABC transporters in prostate cancer (PCa) development, the profile of ABC transporter gene expression was analyzed in PCa and noncancerous prostate tissues (NPT). METHODS: TaqMan Low Density Array (TLDA) human ABC transporter plates were used for the gene expression profiling in 10 PCa and 6 NPT specimens. ABCB1 transcript level was evaluated in a larger set of PCa cases (N = 78) and NPT (N = 15) by real-time PCR, the same PCa cases were assessed for the gene promoter hypermethylation by methylation-specific PCR. RESULTS: Expression of eight ABC transporter genes (ABCA8, ABCB1, ABCC6, ABCC9, ABCC10, ABCD2, ABCG2, and ABCG4) was significantly down-regulated in PCa as compared to NPT, and only two genes (ABCC4 and ABCG1) were up-regulated. Down-regulation of ABC transporter genes was prevalent in the TMPRSS2-ERG-negative cases. A detailed analysis of ABCB1 expression confirmed TLDA results: a reduced level of the transcript was identified in PCa in comparison to NPT (p = 0.048). Moreover, the TMPRSS2-ERG-negative PCa cases showed significantly lower expression of ABCB1 in comparison to NPT (p = 0.003) or the fusion-positive tumors (p = 0.002). Promoter methylation of ABCB1 predominantly occurred in PCa and was rarely detected in NPT (p < 0.001). CONCLUSIONS: The study suggests frequent down-regulation of the ABC transporter genes in PCa, especially in the TMPRSS2-ERG-negative tumors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1689-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-46038412015-10-14 Frequent down-regulation of ABC transporter genes in prostate cancer Demidenko, Rita Razanauskas, Deividas Daniunaite, Kristina Lazutka, Juozas Rimantas Jankevicius, Feliksas Jarmalaite, Sonata BMC Cancer Research Article BACKGROUND: ATP-binding cassette (ABC) transporters are transmembrane proteins responsible for the efflux of a wide variety of substrates, including steroid metabolites, through the cellular membranes. For better characterization of the role of ABC transporters in prostate cancer (PCa) development, the profile of ABC transporter gene expression was analyzed in PCa and noncancerous prostate tissues (NPT). METHODS: TaqMan Low Density Array (TLDA) human ABC transporter plates were used for the gene expression profiling in 10 PCa and 6 NPT specimens. ABCB1 transcript level was evaluated in a larger set of PCa cases (N = 78) and NPT (N = 15) by real-time PCR, the same PCa cases were assessed for the gene promoter hypermethylation by methylation-specific PCR. RESULTS: Expression of eight ABC transporter genes (ABCA8, ABCB1, ABCC6, ABCC9, ABCC10, ABCD2, ABCG2, and ABCG4) was significantly down-regulated in PCa as compared to NPT, and only two genes (ABCC4 and ABCG1) were up-regulated. Down-regulation of ABC transporter genes was prevalent in the TMPRSS2-ERG-negative cases. A detailed analysis of ABCB1 expression confirmed TLDA results: a reduced level of the transcript was identified in PCa in comparison to NPT (p = 0.048). Moreover, the TMPRSS2-ERG-negative PCa cases showed significantly lower expression of ABCB1 in comparison to NPT (p = 0.003) or the fusion-positive tumors (p = 0.002). Promoter methylation of ABCB1 predominantly occurred in PCa and was rarely detected in NPT (p < 0.001). CONCLUSIONS: The study suggests frequent down-regulation of the ABC transporter genes in PCa, especially in the TMPRSS2-ERG-negative tumors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1689-8) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-12 /pmc/articles/PMC4603841/ /pubmed/26459268 http://dx.doi.org/10.1186/s12885-015-1689-8 Text en © Demidenko et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Demidenko, Rita
Razanauskas, Deividas
Daniunaite, Kristina
Lazutka, Juozas Rimantas
Jankevicius, Feliksas
Jarmalaite, Sonata
Frequent down-regulation of ABC transporter genes in prostate cancer
title Frequent down-regulation of ABC transporter genes in prostate cancer
title_full Frequent down-regulation of ABC transporter genes in prostate cancer
title_fullStr Frequent down-regulation of ABC transporter genes in prostate cancer
title_full_unstemmed Frequent down-regulation of ABC transporter genes in prostate cancer
title_short Frequent down-regulation of ABC transporter genes in prostate cancer
title_sort frequent down-regulation of abc transporter genes in prostate cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603841/
https://www.ncbi.nlm.nih.gov/pubmed/26459268
http://dx.doi.org/10.1186/s12885-015-1689-8
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