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Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target

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dc.title Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target en
dc.contributor.author Brynychová, Veronika
dc.contributor.author Hlaváč, Viktor
dc.contributor.author Ehrlichová, Marie
dc.contributor.author Václavíková, Radka
dc.contributor.author Němcová-Fürstová, Vlasta
dc.contributor.author Pecha, Václav
dc.contributor.author Trnková, Markéta
dc.contributor.author Mrhalová, Marcela
dc.contributor.author Kodet, Roman
dc.contributor.author Vrána, David
dc.contributor.author Gatěk, Jiří
dc.contributor.author Bendová, Marie
dc.contributor.author Vernerová, Zdeňka
dc.contributor.author Kovář, Jan
dc.contributor.author Souček, Pavel
dc.relation.ispartof Clinical Chemistry and Laboratory Medicine
dc.identifier.issn 1434-6621 Scopus Sources, Sherpa/RoMEO, JCR
dc.date.issued 2017
utb.relation.volume 55
utb.relation.issue 1
dc.citation.spage 111
dc.citation.epage 122
dc.type article
dc.language.iso en
dc.publisher Walter de Gruyter GmbH
dc.identifier.doi 10.1515/cclm-2016-0271
dc.subject alternative splicing en
dc.subject breast carcinoma en
dc.subject caspases en
dc.subject prognosis en
dc.subject transcript en
dc.description.abstract Background: Apoptosis plays a critical role in cancer cell survival and tumor development. We provide a hypothesis- generating screen for further research by exploring the expression profile and genetic variability of caspases (2, 3, 7, 8, 9, and 10) in breast carcinoma patients. This study addressed isoform-specific caspase transcript expression and genetic variability in regulatory sequences of caspases 2 and 9. Methods: Gene expression profiling was performed by quantitative real-time PCR in tumor and paired non-malignant tissues of two independent groups of patients. Genetic variability was determined by high resolution melting, allelic discrimination, and sequencing analysis in tumor and peripheral blood lymphocyte DNA of the patients. Results: CASP3 A+ B and S isoforms were over-expressed in tumors of both patient groups. The CASP9 transcript was down-regulated in tumors of both groups of patients and significantly associated with expression of hormonal receptors and with the presence of rs4645978-rs2020903rs4646034 haplotype in the CASP9 gene. Patients with a low intratumoral CASP9A/B isoform expression ratio (predicted to shift equilibrium towards anti-apoptotic isoform) subsequently treated with adjuvant chemotherapy had a significantly shorter disease-free survival than those with the high ratio (p = 0.04). Inheritance of CC genotype of rs2020903 in CASP9 was associated with progesterone receptor expression in tumors (p = 0.003). Conclusions: Genetic variability in CASP9 and expression of its splicing variants present targets for further study. en
utb.faculty Faculty of Humanities
dc.identifier.uri http://hdl.handle.net/10563/1006847
utb.identifier.obdid 43877897
utb.identifier.scopus 2-s2.0-84998694303
utb.identifier.wok 000388930700021
utb.identifier.pubmed 27327132
utb.identifier.coden CCLMF
utb.source j-wok
dc.date.accessioned 2017-02-28T15:11:32Z
dc.date.available 2017-02-28T15:11:32Z
dc.description.sponsorship CU Grant Agency [1444313]; MH CZ - DRO (National Institute of Public Health - NIPH) project [75010330]; Internal Grant Agency of the Czech Ministry of Health [14055-3]
utb.contributor.internalauthor Gatěk, Jiří
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