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dc.contributor.authorPérez Fusté, Noel
dc.contributor.authorCastelblanco Echavarría, Esmeralda
dc.contributor.authorFelip, Isidre
dc.contributor.authorSantacana Espasa, Maria
dc.contributor.authorFernández Hernández, Rita
dc.contributor.authorGatius Calderó, Sònia
dc.contributor.authorPedraza González, Neus
dc.contributor.authorPallares, Judit
dc.contributor.authorCemeli, Tània
dc.contributor.authorValls Marsal, Joan
dc.contributor.authorTarres, Marc
dc.contributor.authorFerrezuelo, Francisco
dc.contributor.authorDolcet Roca, Xavier
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorGarí Marsol, Eloi
dc.description.abstractCyclin D1 (Ccnd1) is a proto-oncogen amplified in many different cancers and nuclear accumulation of Ccnd1 is a characteristic of tumor cells. Ccnd1 activates the transcription of a large set of genes involved in cell cycle progress and proliferation. However, Ccnd1 also targets cytoplasmic proteins involved in the regulation of cell migration and invasion. In this work, we have analyzed by immunohistochemistry the localization of Ccnd1 in endometrial, breast, prostate and colon carcinomas with different types of invasion. The number of cells displaying membranous or cytoplasmic Ccnd1 was significantly higher in peripheral cells than in inner cells in both collective and pushing invasion patterns of endometrial carcinoma, and in collective invasion pattern of colon carcinoma. Also, the cytoplasmic localization of Ccnd1 was higher when tumors infiltrated as single cells, budding or small clusters of cells. To evaluate cytoplasmic function of cyclin D1, we have built a variant (Ccnd1-CAAX) that remains attached to the cell membrane therefore sequestering this cyclin in the cytoplasm. Tumor cells harboring Ccnd1-CAAX showed high levels of invasiveness and metastatic potential compared to those containing the wild type allele of Ccnd1. However, Ccnd1- CAAX expression did not alter proliferative rates of tumor cells. We hypothesize that the role of Ccnd1 in the cytoplasm is mainly associated with the invasive capability of tumor cells. Moreover, we propose that subcellular localization of Ccnd1 is an interesting guideline to measure cancer outcome.ca_ES
dc.description.sponsorshipThis work was funded by Spanish Ministry of Education and Science (BFU2010-20293/ BMC and BFU2013-42895-P), Catalan Government (SGR-559), and Fondo de Investigaciones Sanitarias (PI10/00604 and PI13/00263). X.M-G was supported by grants 2014SGR138, RD12/0036/0013, and Fundación Asociación Española contra el Cancer. Tumour samples were obtained with the support of Xarxa Catalana de Bancs de Tumors, and Plataforma de Biobancos ISCIII (PT13/0010/0014). NP. Fusté was supported by a contract from “Fundació Alicia Cuello de Merigó”. I. Felip and T. Cemeli were supported by a predoctoral fellowship from FPU-MINECO.ca_ES
dc.publisherImpact Journalsca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofOncotarget, 2016, vol. 7, núm. 19, p. 26979-26991ca_ES
dc.rightscc-by, (c) Impact Journals, 2016ca_ES
dc.subjectCyclin D1ca_ES
dc.subjectTissue arrayca_ES
dc.subjectCell invasionca_ES
dc.titleCharacterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancerca_ES

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