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Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

BACKGROUND: CpG hypermethylation in gene promoters is a frequent mechanism of tumor suppressor gene silencing in various types of cancers. It usually occurs at early steps of cancer progression and can be detected easily, giving rise to development of promising biomarkers for both detection and prog...

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Autores principales: Sayar, Nilufer, Karahan, Gurbet, Konu, Ozlen, Bozkurt, Betul, Bozdogan, Onder, Yulug, Isik G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587865/
https://www.ncbi.nlm.nih.gov/pubmed/26421063
http://dx.doi.org/10.1186/s13148-015-0138-5
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author Sayar, Nilufer
Karahan, Gurbet
Konu, Ozlen
Bozkurt, Betul
Bozdogan, Onder
Yulug, Isik G.
author_facet Sayar, Nilufer
Karahan, Gurbet
Konu, Ozlen
Bozkurt, Betul
Bozdogan, Onder
Yulug, Isik G.
author_sort Sayar, Nilufer
collection PubMed
description BACKGROUND: CpG hypermethylation in gene promoters is a frequent mechanism of tumor suppressor gene silencing in various types of cancers. It usually occurs at early steps of cancer progression and can be detected easily, giving rise to development of promising biomarkers for both detection and progression of cancer, including breast cancer. 5-aza-2′-deoxycytidine (AZA) is a DNA demethylating and anti-cancer agent resulting in induction of genes suppressed via DNA hypermethylation. RESULTS: Using microarray expression profiling of AZA- or DMSO-treated breast cancer and non-tumorigenic breast (NTB) cells, we identified for the first time TAGLN gene as a target of DNA hypermethylation in breast cancer. TAGLN expression was significantly and frequently downregulated via promoter DNA hypermethylation in breast cancer cells compared to NTB cells, and also in 13/21 (61.9 %) of breast tumors compared to matched normal tissues. Analyses of public microarray methylation data showed that TAGLN was also hypermethylated in 63.02 % of tumors compared to normal tissues; relapse-free survival of patients was worse with higher TAGLN methylation; and methylation levels could discriminate between tumors and healthy tissues with 83.14 % sensitivity and 100 % specificity. Additionally, qRT-PCR and immunohistochemistry experiments showed that TAGLN expression was significantly downregulated in two more independent sets of breast tumors compared to normal tissues and was lower in tumors with poor prognosis. Colony formation was increased in TAGLN silenced NTB cells, while decreased in overexpressing BC cells. CONCLUSIONS: TAGLN gene is frequently downregulated by DNA hypermethylation, and TAGLN promoter methylation profiles could serve as a future diagnostic biomarker, with possible clinical impact regarding the prognosis in breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-015-0138-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-45878652015-09-30 Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer Sayar, Nilufer Karahan, Gurbet Konu, Ozlen Bozkurt, Betul Bozdogan, Onder Yulug, Isik G. Clin Epigenetics Research BACKGROUND: CpG hypermethylation in gene promoters is a frequent mechanism of tumor suppressor gene silencing in various types of cancers. It usually occurs at early steps of cancer progression and can be detected easily, giving rise to development of promising biomarkers for both detection and progression of cancer, including breast cancer. 5-aza-2′-deoxycytidine (AZA) is a DNA demethylating and anti-cancer agent resulting in induction of genes suppressed via DNA hypermethylation. RESULTS: Using microarray expression profiling of AZA- or DMSO-treated breast cancer and non-tumorigenic breast (NTB) cells, we identified for the first time TAGLN gene as a target of DNA hypermethylation in breast cancer. TAGLN expression was significantly and frequently downregulated via promoter DNA hypermethylation in breast cancer cells compared to NTB cells, and also in 13/21 (61.9 %) of breast tumors compared to matched normal tissues. Analyses of public microarray methylation data showed that TAGLN was also hypermethylated in 63.02 % of tumors compared to normal tissues; relapse-free survival of patients was worse with higher TAGLN methylation; and methylation levels could discriminate between tumors and healthy tissues with 83.14 % sensitivity and 100 % specificity. Additionally, qRT-PCR and immunohistochemistry experiments showed that TAGLN expression was significantly downregulated in two more independent sets of breast tumors compared to normal tissues and was lower in tumors with poor prognosis. Colony formation was increased in TAGLN silenced NTB cells, while decreased in overexpressing BC cells. CONCLUSIONS: TAGLN gene is frequently downregulated by DNA hypermethylation, and TAGLN promoter methylation profiles could serve as a future diagnostic biomarker, with possible clinical impact regarding the prognosis in breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-015-0138-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-28 /pmc/articles/PMC4587865/ /pubmed/26421063 http://dx.doi.org/10.1186/s13148-015-0138-5 Text en © Sayar 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
Sayar, Nilufer
Karahan, Gurbet
Konu, Ozlen
Bozkurt, Betul
Bozdogan, Onder
Yulug, Isik G.
Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer
title Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer
title_full Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer
title_fullStr Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer
title_full_unstemmed Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer
title_short Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer
title_sort transgelin gene is frequently downregulated by promoter dna hypermethylation in breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587865/
https://www.ncbi.nlm.nih.gov/pubmed/26421063
http://dx.doi.org/10.1186/s13148-015-0138-5
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