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DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.

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dc.contributor.authorMartinez-Useros, Javier
dc.contributor.authorRodriguez-Remirez, Maria
dc.contributor.authorBorrero-Palacios, Aurea
dc.contributor.authorMoreno, Irene
dc.contributor.authorCebrian, Arancha
dc.contributor.authorGomez del Pulgar, Teresa
dc.contributor.authordel Puerto-Nevado, Laura
dc.contributor.authorVega-Bravo, Ricardo
dc.contributor.authorPuime-Otin, Alberto
dc.contributor.authorPerez, Nuria
dc.contributor.authorZazo, Sandra
dc.contributor.authorSenin, Clara
dc.contributor.authorFernandez-Aceñero, Maria J
dc.contributor.authorSoengas, MS
dc.contributor.authorRojo, Federico
dc.contributor.authorGarcia-Foncillas, Jesus
dc.contributor.funderInstituto de Salud Carlos III
dc.date.accessioned2024-11-04T13:07:48Z
dc.date.available2024-11-04T13:07:48Z
dc.date.issued2014-12-16
dc.descriptionWe thank Dr. Carlos Pastor from Surgery Department from Fundacion Jimenez-Diaz Hospital (Madrid, Spain) for providing us human samples, and Dr. Juan Valcarcel from Centre of Genomic Regulation (Barcelona, Spain) for his appreciated leadership of the CONSOLIDER-Consortium. This work has been carried out with the support of the RNA-Reg. CONSOLIDER-Consortium (CSD2009-00080) and by grants: RD12/0036/0051, RD09/0076/0101, PI12/01552 from Spanish Institute of Health Carlos III (ISCIII) and S2010/BMD2344.
dc.description.abstractDEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures. It plays an important role in development and progression of different types of cancer. This study aims to analyze the role of DEK in metastatic colorectal cancer.
dc.description.abstractBaseline DEK expression was firstly quantified in 9 colorectal cell lines and normal mucosa by WB. SiRNA-mediated DEK inhibition was carried out for transient DEK silencing in DLD1 and SW620 to dissect its role in colorectal cancer aggressiveness. Irinotecan response assays were performed with SN38 over 24 hours and apoptosis was quantified by flow cytometry. Ex-vivo assay was carried out with 3 fresh tumour tissues taken from surgical resection and treated with SN38 for 24 hours. DEK expression was determined by immunohistochemistry in 67 formalin-fixed paraffin-embedded tumour samples from metastatic colorectal cancer patients treated with irinotecan-based therapy as first-line treatment.
dc.description.abstractThe DEK oncogene is overexpressed in all colorectal cancer cell lines. Knock-down of DEK on DLD1 and SW620 cell lines decreased cell migration and increased irinotecan-induced apoptosis. In addition, low DEK expression level predicted irinotecan-based chemotherapy response in metastatic colorectal cancer patients with KRAS wild-type.
dc.description.abstractThese data suggest DEK overexpression as a crucial event for the emergence of an aggressive phenotype in colorectal cancer and its potential role as biomarker for irinotecan response in those patients with KRAS wild-type status.
dc.description.peerreviewedSí
dc.format.page965
dc.format.volume14
dc.identifier.citationBMC Cancer . 2014 Dec 16:14:965.
dc.identifier.journalBMC Cancer
dc.identifier.pubmedID25515240
dc.identifier.urihttps://hdl.handle.net/20.500.12105/25424
dc.language.isoeng
dc.publisherBioMed Central (BMC)
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//PI12%2F01552/ES/Identificación de mecanismos de resistencia a nuevos anticuerpos anti-HER2 en cáncer de mama/
dc.relation.projectIDinfo:eu-repo/grantAgreement/MICINN//CSD2009-00080/ES/An integrated approach to post-transcriptional regulation of gene expression and its role in human disease/
dc.relation.publisherversionhttp://www.10.1186/1471-2407-14-965
dc.repisalud.institucionCNIO
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Melanoma
dc.rights.accessRightsopen access
dc.rights.licenseAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectDEK
dc.subjectIrinotecan
dc.subjectAggressive phenotype
dc.subjectMetastatic colorectal cancer
dc.subjectKRAS
dc.titleDEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication
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