RT info:eu-repo/semantics/article
T1 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.
A1 Gil-Araujo, Beatriz
A1 Gutiérrez-Salmerón, María
A1 Gutiérrez-Pitalúa, Julia
A1 Angulo Cuesta, Javier
A1 Lasa Benito, Marina
A1 Toledo Lobo, María del Val
A1 Ropero Salinas, Santiago
A1 Chiloeches Gálvez, Antonio
K1 Dual specificity phosphatase 1
K1 NF-kB
K1 Apoptosis
K1 p38 MAPK
K1 Prostate cancer
K1 Bioquímica
K1 Biochemistry
K1 Apoptosis
K1 Cell Line, Tumor
K1 Dual Specificity Phosphatase 1
K1 Gene Expression Regulation, Neoplastic
K1 Humans
K1 Male
K1 NF-kappa B
K1 Phosphorylation
K1 Prostate
K1 Prostatic Neoplasms
K1 Signal Transduction
K1 p38 Mitogen-Activated Protein Kinases
AB 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.
PB Elsevier
SN 1574-7891
YR 2014
FD 2014-02
LK http://hdl.handle.net/10017/33641
UL http://hdl.handle.net/10017/33641
LA eng
NO Fondo de Investigaciones Sanitarias
DS MINDS@UW
RD 20-abr-2024