dc.contributor.author | Gil-Araujo, Beatriz | |
dc.contributor.author | Gutiérrez-Salmerón, María | |
dc.contributor.author | Gutiérrez-Pitalúa, Julia | |
dc.contributor.author | Angulo Cuesta, Javier | |
dc.contributor.author | Lasa Benito, Marina | |
dc.contributor.author | Toledo Lobo, María del Val | |
dc.contributor.author | Ropero Salinas, Santiago | |
dc.contributor.author | Chiloeches Gálvez, Antonio | |
dc.date.accessioned | 2018-06-29T15:35:17Z | |
dc.date.available | 2018-06-29T15:35:17Z | |
dc.date.issued | 2014-02 | |
dc.identifier.bibliographicCitation | Molecular Oncology, 2014, v. 8, n. 1, p. 27-38 | en |
dc.identifier.issn | 1574-7891 | |
dc.identifier.uri | http://hdl.handle.net/10017/33641 | |
dc.description.abstract | Dual specificity phosphatase 1 (DUSP1) and the transcription factor NF-κB are implicated in prostate cancer since their expression levels are altered along this disease, although there are no evidences up to date demonstrating a crosstalk between them. In this report, we show for the first time that DUSP1 over-expression in DU145 cells promotes apoptosis and decreases NF-κB activity by blocking p65/NF-κB nuclear translocation. Moreover, although DUSP1 impairs TNF-α-induced p38 MAPK and JNK activation, only the specific inhibition of p38 MAPK exerts the same effects than DUSP1 over-expression on both apoptosis and NF-κB activity. Consistently, DUSP1 promotes apoptosis and decreases NF-κB activity in cells in which p38 MAPK is induced by TNF-α treatment. These results demonstrate that p38 MAPK is specifically involved in DUSP1-mediated effects on both apoptosis and NF-κB activity. Interestingly, we show an inverse correlation between DUSP1 expression and activation of both p65/NF-κB and p38 MAPK in human prostate tissue specimens. Thus, most of apparently normal glands, benign prostatic hyperplasia and low-grade prostatic intraepithelial neoplasia samples show high DUSP1 expression and low levels of both nuclear p65/NF-κB and activated p38 MAPK. By contrast, DUSP1 expression levels are low or even absent in high-grade prostatic intraepithelial neoplasia and prostatic adenocarcinoma samples, whereas nuclear p65/NF-κB and activated p38 MAPK are highly expressed in the same samples. Overall, our results provide evidence for a role of DUSP1 in the apoptosis of prostate cancer cells, through a mechanism involving the inhibition of p38 MAPK and NF-κB. Furthermore, our findings suggest that the ratio between DUSP1 and p65/NF-κB expression levels, rather than the individual expression of both molecules, is a better marker for diagnostic purposes in prostate cancer. | en |
dc.description.sponsorship | Fondo de Investigaciones Sanitarias | es_ES |
dc.description.sponsorship | Ministerio de Economía y Competitividad | es_ES |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.publisher | Elsevier | en |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional(c) Federation of European Biochemical Societies, 2013 | en |
dc.rights | (c) Federation of European Biochemical Societies, 2013 | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
dc.subject | Dual specificity phosphatase 1 | en |
dc.subject | NF-kB | en |
dc.subject | Apoptosis | en |
dc.subject | p38 MAPK | en |
dc.subject | Prostate cancer | en |
dc.title | Dual specificity phosphatase 1 expression inversely correlates with NF-κB activity and expression in prostate cancer and promotes apoptosis through a p38 MAPK dependent mechanism. | en |
dc.type | info:eu-repo/semantics/article | en |
dc.subject.eciencia | Bioquímica | es_ES |
dc.subject.eciencia | Biochemistry | en |
dc.contributor.affiliation | Universidad de Alcalá. Departamento de Biología de Sistemas | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.identifier.doi | 10.1016/j.molonc.2013.08.012 | |
dc.relation.projectID | info:eu-repo/grantAgreement/MINECO//PI07%2F0832/ES | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | en |
dc.identifier.publicationtitle | Molecular oncology | en |
dc.identifier.publicationvolume | 8 | |
dc.identifier.publicationlastpage | 38 | |
dc.identifier.publicationissue | 1 | |
dc.identifier.publicationfirstpage | 27 | |
dc.identifier.pmid | 24080497 | |
dc.subject.mesh | Apoptosis | en |
dc.subject.mesh | Cell Line, Tumor | en |
dc.subject.mesh | Dual Specificity Phosphatase 1 | en |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | en |
dc.subject.mesh | Humans | en |
dc.subject.mesh | Male | en |
dc.subject.mesh | NF-kappa B | en |
dc.subject.mesh | Phosphorylation | en |
dc.subject.mesh | Prostate | en |
dc.subject.mesh | Prostatic Neoplasms | en |
dc.subject.mesh | Signal Transduction | en |
dc.subject.mesh | p38 Mitogen-Activated Protein Kinases | en |
dc.identifier.essn | 1878-0261 | |