%0 Journal Article %A Gil-Araujo, Beatriz %A Gutiérrez-Salmerón, María %A Gutiérrez-Pitalúa, Julia %A Angulo Cuesta, Javier %A Lasa Benito, Marina %A Toledo Lobo, María del Val %A Ropero Salinas, Santiago %A Chiloeches Gálvez, Antonio %T 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. %D 2014 %@ 1574-7891 %U http://hdl.handle.net/10017/33641 %X 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. %K Dual specificity phosphatase 1 %K NF-kB %K Apoptosis %K p38 MAPK %K Prostate cancer %K Bioquímica %K Biochemistry %K Apoptosis %K Cell Line, Tumor %K Dual Specificity Phosphatase 1 %K Gene Expression Regulation, Neoplastic %K Humans %K Male %K NF-kappa B %K Phosphorylation %K Prostate %K Prostatic Neoplasms %K Signal Transduction %K p38 Mitogen-Activated Protein Kinases %~ Biblioteca Universidad de Alcala