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.
AuthorGil-Araujo, Beatriz; Gutiérrez-Salmerón, María; Gutiérrez-Pitalúa, Julia; Angulo Cuesta, Javier; Lasa Benito, Marina; [et al.]
IdentifiersEnlace permanente (URI): http://hdl.handle.net/10017/33641
Fondo de Investigaciones Sanitarias
Molecular Oncology, 2014, v. 8, n. 1, p. 27-38
Dual specificity phosphatase 1
PI070832 (Fondo de Investigaciones Sanitarias)
Tipo de documento
Attribution-NonCommercial-NoDerivatives 4.0 Internacional(c) Federation of European Biochemical Societies, 2013
(c) Federation of European Biochemical Societies, 2013
Derechos de acceso
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.
Files in this item
- BIOQBM - Artículos