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

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dc.citation.epage16en_US
dc.citation.issueNumber1en_US
dc.citation.spage1en_US
dc.citation.volumeNumber7en_US
dc.contributor.authorSayar, N.en_US
dc.contributor.authorKarahan, G.en_US
dc.contributor.authorKonu, O.en_US
dc.contributor.authorBozkurt, B.en_US
dc.contributor.authorBozdogan, O.en_US
dc.contributor.authorYulug, I. G.en_US
dc.date.accessioned2019-02-10T20:40:08Z
dc.date.available2019-02-10T20:40:08Z
dc.date.issued2015-09-28en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractBackground: 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.en_US
dc.description.provenanceSubmitted by M. Arif Kart (arif.kart@bilkent.edu.tr) on 2019-02-10T20:40:08Z No. of bitstreams: 1 Transgelin_gene_is_frequently_downregulated_by_promoter_DNA_hypermethylation_in_breast_cancer.pdf: 3270249 bytes, checksum: b32db06a9902974193f8736c9ccce2c8 (MD5)en
dc.description.provenanceMade available in DSpace on 2019-02-10T20:40:08Z (GMT). No. of bitstreams: 1 Transgelin_gene_is_frequently_downregulated_by_promoter_DNA_hypermethylation_in_breast_cancer.pdf: 3270249 bytes, checksum: b32db06a9902974193f8736c9ccce2c8 (MD5) Previous issue date: 2015-09-28en
dc.identifier.doi10.1186/s13148-015-0138-5en_US
dc.identifier.issn1868-7083
dc.identifier.urihttp://hdl.handle.net/11693/49185
dc.language.isoEnglishen_US
dc.publisherSpringeren_US
dc.relation.isversionofhttps://doi.org/10.1186/s13148-015-0138-5en_US
dc.source.titleClinical Epigeneticsen_US
dc.subjectDNA methylationen_US
dc.subjectHypermethylationen_US
dc.subjectBreast canceren_US
dc.subjectTAGLNen_US
dc.subjectSM22 alphaen_US
dc.subjectPrognosisen_US
dc.subjectDiagnosisen_US
dc.titleTransgelin gene is frequently downregulated by promoter DNA hypermethylation in breast canceren_US
dc.typeArticleen_US

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