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dc.contributor.author | Leandro-García, Luis J | |
dc.contributor.author | Leskelä, Susanna | |
dc.contributor.author | Inglada-Pérez, Lucía | |
dc.contributor.author | Landa, Iñigo | |
dc.contributor.author | de Cubas, Aguirre A | |
dc.contributor.author | Maliszewska, Agnieszka | |
dc.contributor.author | Comino-Méndez, Iñaki | |
dc.contributor.author | Letón, Rocío | |
dc.contributor.author | Gómez-Graña, Álvaro | |
dc.contributor.author | Torres, Raúl | |
dc.contributor.author | Ramírez, Juan Carlos | |
dc.contributor.author | Álvarez, Sara | |
dc.contributor.author | Rivera, José | |
dc.contributor.author | Martínez, Constantino | |
dc.contributor.author | Lozano, María Luisa | |
dc.contributor.author | Cascón, Alberto | |
dc.contributor.author | Robledo Batanero, Mercedes | |
dc.contributor.author | Rodriguez Antona, Cristina | |
dc.date.accessioned | 2024-02-06T09:43:52Z | |
dc.date.available | 2024-02-06T09:43:52Z | |
dc.date.issued | 2012-09-15 | |
dc.identifier.citation | Cancer Res . 2012 ;72(18):4744-52. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/17499 | |
dc.description.abstract | Cellular microtubules composed of α-β-tubulin heterodimers that are essential for cell shape, division, and intracellular transport are valid targets for anticancer therapy. However, not all the conserved but differentially expressed members of the β-tubulin gene superfamily have been investigated for their role in these settings. In this study, we examined roles for the hematologic isoform β-tubulin VI and functional genetic variants in the gene. β-tubulin VI was highly expressed in blood cells with a substantial interindividual variability (seven-fold variation in mRNA). We characterized DNA missense variations leading to Q43P, T274M, and R307H, and a rare nonsense variant, Y55X. Because variations in the hematologic target of microtubule-binding drugs might alter their myelosuppressive action, we tested their effect in cell lines stably expressing the different β-tubulin VI full-length variants, finding that the T274M change significantly decreased sensitivity to paclitaxel-induced tubulin polymerization. Furthermore, patients treated with paclitaxel and carrying β-tubulin VI T274M exhibited a significantly lower thrombocytopenia than wild-type homozygous patients (P = 0.031). Together, our findings define β-tubulin VI as a hematologic isotype with significant genetic variation in humans that may affect the myelosuppresive action of microtubule-binding drugs. A polymorphism found in a tubulin isoform expressed only in hemapoietic cells may contribute to the patient variation in myelosuppression that occurs after treatment with microtubule-binding drugs. | es_ES |
dc.description.sponsorship | This article was supported by a project from the Spanish Ministry of Science and Innovation (SAF2009-08307). L. J. Leandro-Garcia was supported by a FIS fellowship (FI08/00375) and Susanna Leskela by a fellowship from the Spanish Ministry of Science and Innovation (AP2005-4514). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Association for Cancer Research (AACR) | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Antineoplastic Agents | es_ES |
dc.subject.mesh | Genetic Predisposition to Disease | es_ES |
dc.subject.mesh | Genotype | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Microtubules | es_ES |
dc.subject.mesh | Paclitaxel | es_ES |
dc.subject.mesh | Polymorphism, Single Nucleotide | es_ES |
dc.subject.mesh | Protein Isoforms | es_ES |
dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | es_ES |
dc.subject.mesh | Thrombocytopenia | es_ES |
dc.subject.mesh | Tubulin | es_ES |
dc.title | Hematologic β-tubulin VI isoform exhibits genetic variability that influences paclitaxel toxicity. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 22805305 | es_ES |
dc.format.volume | 72 | es_ES |
dc.format.number | 18 | es_ES |
dc.format.page | 4744 | es_ES |
dc.identifier.doi | 10.1158/0008-5472.CAN-11-2861 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1538-7445 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1158/0008-5472. | es_ES |
dc.identifier.journal | Cancer research | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Cáncer Endocrino Hereditario | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/FI08/00375 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/SAF2009-08307 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/AP2005-4514 | es_ES |